Pathway effects
| Receptor | Ligand | Pathway | Therapeutic area | Pathway effect outcome | Experiment | Reference | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Class
| Rec Fam
| UniProt
| GtP
| Species
| Name
| Effector
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| Effect type
| High level term
| Summary
| Details
| Pathway distinction
| System
| Method
| Authors
| DOI
| |
Receptor | Ligand | Pathway | Therapeutic area | Pathway effect outcome | Experiment | Reference | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Class
| Rec Fam
| UniProt
| GtP
| Species
| Name
| Effector
|
| Effect type
| High level term
| Summary
| Details
| Pathway distinction
| System
| Method
| Authors
| DOI
| |
| 93198 | A | Opioid receptors | OPRM | μ | Mouse | OLICERIDINE | g protein | opioid analgesia and side effects | analgesia | Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. | TRV130 induced rapid and powerful analgesia in mouse hot plate study. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD | 344:708-17 | |
| 93198 | A | Opioid receptors | OPRM | μ | Rat | OLICERIDINE | g protein | opioid analgesia and side effects | analgesia | Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. | TRV130 induced rapid and powerful analgesia in rat hot plate, tail flick, and incisional pain study. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD | 344:708-17 | |
| 93198 | A | Opioid receptors | OPRM | μ | Mouse | OLICERIDINE | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. | TRV130 induced less gastrointestinal dysfunction than morphine at equivalent doses in mouse glass bead colonic motility and fecal boli assay. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD | 344:708-17 | |
| 93198 | A | Opioid receptors | OPRM | μ | Rat | OLICERIDINE | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. | TRV130 induced less gastrointestinal dysfunction than morphine at equivalent doses in rat glass bead colonic motility and fecal boli assay. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD | 344:708-17 | |
| 93198 | A | Opioid receptors | OPRM | μ | Rat | OLICERIDINE | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | Biased ligand induced analgesia with reduced gastrointestinal and respiratory dysfunction compared to morphine. | TRV130 showed increased analgesia vs. Respiratory suppression and sedation in rat arterial blood gas measurement. | Biased ligand (towards sig. prot.) | Animals | Blood analysis | DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD | 344:708-17 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | g protein | opioid analgesia and side effects | analgesia | TRV130 produced significantly greater categorical pain relief than morphine after first dose, no serious adverse effects and tolerability similar to morphine. | Biased ligand showed significant reduction of pain intensity over 49 hours compared with placebo | Biased ligand (towards sig. prot.) | Humans | Numeric rating scales (pain intensity, etc.) | Viscusi ER, Webster L, Kuss M, Daniels S, Bolognese JA, Zuckerman S, Soergel DG, Subach RA, Cook E, Skobieranda F | 157:264-272 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | TRV130 produced significantly greater categorical pain relief than morphine after first dose, no serious adverse effects and tolerability similar to morphine. | Biased ligand showed dose-related opioid related adverse effects, most commonly nausea, dizziness, headache, and vomiting. | Biased ligand (towards sig. prot.) | Humans | Open-ended questions (report of AEs) | Viscusi ER, Webster L, Kuss M, Daniels S, Bolognese JA, Zuckerman S, Soergel DG, Subach RA, Cook E, Skobieranda F | 157:264-272 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | g protein | opioid analgesia and side effects | analgesia | TRV130 provides rapid analgesia compared to placebo and has a favorable sefety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine. | Biased ligand provides rapid analgesia for the relief of moderate-to-severe acute postoperative pain. | Biased ligand (towards sig. prot.) | Humans | Numeric rating scales (pain intensity, etc.) | Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N | 12:927-943 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | TRV130 provides rapid analgesia compared to placebo and has a favorable sefety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine. | Biased ligand showed significant lower odds ratio for antiemetic use in TRV130 regimes compared to morphine. | Biased ligand (towards sig. prot.) | Humans | Use of rescue medication (e.g. antiemetic or pain meds) | Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N | 12:927-943 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | TRV130 provides rapid analgesia compared to placebo and has a favorable sefety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine. | Biased ligand showed favorable safety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine. | Biased ligand (towards sig. prot.) | Humans | Physical examination | Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N | 12:927-943 | |
| A | Opioid receptors | OPRM | μ | Mouse | - | g protein | opioid analgesia and side effects | analgesia | Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. | Phosphorylation-deficient MOR mice showed an increase of analgesic potency of opioids in hot plate studies. | Knock in - mutant receptor with impared signalling | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S | 10:367 | ||
| A | Opioid receptors | OPRM | μ | Mouse | - | g protein | opioid analgesia and side effects | side effects of opioids | Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. | Opioids induced respiratory depression in all mutant receptor mice measured by plethysmography. | Knock in - mutant receptor with impared signalling | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S | 10:367 | ||
| A | Opioid receptors | OPRM | μ | Mouse | - | g protein | opioid analgesia and side effects | side effects of opioids | Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. | Opioids induced constipation in all mutant receptor mice measured by accumulated fecal boli quantification. | Knock in - mutant receptor with impared signalling | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S | 10:367 | ||
| A | Opioid receptors | OPRM | μ | Mouse | - | g protein | opioid analgesia and side effects | side effects of opioids | Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. | Mice display typical signs of withdrawal including jumping, wet-dog shakes and grooming with no significant difference between receptor phenotypes. Observation of behavior followed naloxone injection. | Knock in - mutant receptor with impared signalling | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S | 10:367 | ||
| A | Opioid receptors | OPRM | μ | Mouse | - | β-arrestin | opioid analgesia and side effects | side effects of opioids | Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. | Desensitization of MOR coupling to GIRK channels in locus coeruleus neurons from horizontal brain sections of mice from all receptor genotypes. | Knock in - mutant receptor with impared signalling | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S | 10:367 | ||
| A | Opioid receptors | OPRM | μ | Mouse | - | β-arrestin | opioid analgesia and side effects | side effects of opioids | Phosphorylation-deficient G protein biased MOR receptors improve analgesia and diminish tolerance but worsen opioid side effects. | Mutant receptor mice show no significant shift in sensitivity in hot plate study after 7 days of constant opioid exposure. | Knock in - mutant receptor with impared signalling | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ, Schulz S | 10:367 | ||
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | gi/o-family | opioid analgesia and side effects | analgesia | PZM21 is mor efficacious for the affective component of analgesia vs. The reflexive component and is devoid of respiratory depression and morphine-like reinforcing activity at equi-analgesic doses. | Biased ligand shows analgesia (specific for central over reflex analgesia) in mice hot plate, tail-flick and formalin injection studies. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK | 537:185-190 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | PZM21 is mor efficacious for the affective component of analgesia vs. The reflexive component and is devoid of respiratory depression and morphine-like reinforcing activity at equi-analgesic doses. | Biased ligand showed no apparent respiratory depression in whole-body plethysmography. | Biased ligand (towards sig. prot.) | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK | 537:185-190 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | PZM21 is mor efficacious for the affective component of analgesia vs. The reflexive component and is devoid of respiratory depression and morphine-like reinforcing activity at equi-analgesic doses. | Biased ligands did not show hyperlocomotion in an open field assay. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK | 537:185-190 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | β-arrestin-2 (non-visual arrestin-3) | opioid analgesia and side effects | side effects of opioids | PZM21 is mor efficacious for the affective component of analgesia vs. The reflexive component and is devoid of respiratory depression and morphine-like reinforcing activity at equi-analgesic doses. | Biased ligand did not induce conditioned place preference in mice. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hubner H, Huang XP, Sassano MF, Giguere PM, Lober S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK | 537:185-190 | |
| 93198 | A | Opioid receptors | OPRM | μ | Mouse | OLICERIDINE | g protein | opioid analgesia and side effects | analgesia | Acute TRV130 treatment produced robust antinociception, complete inhibition of gastrointestinal functionm and weak-abuse-related effects. | Biased ligand showed antinociception without tolerance development in tail-withdrawal study. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Altarifi AA, David B, Muchhala KH, Blough BE, Akbarali H, Negus SS | 31:730-739 | |
| 93198 | A | Opioid receptors | OPRM | μ | Mouse | OLICERIDINE | g protein | opioid analgesia and side effects | side effects of opioids | Acute TRV130 treatment produced robust antinociception, complete inhibition of gastrointestinal functionm and weak-abuse-related effects. | Biased ligand showed suppression of fecal output without tolerance development in fecal boli accumulation assay. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Altarifi AA, David B, Muchhala KH, Blough BE, Akbarali H, Negus SS | 31:730-739 | |
| 93198 | A | Opioid receptors | OPRM | μ | Mouse | OLICERIDINE | g protein | opioid analgesia and side effects | side effects of opioids | Acute TRV130 treatment produced robust antinociception, complete inhibition of gastrointestinal functionm and weak-abuse-related effects. | Biased ligand nearly eliminated colonic propulsion which was measured by video imaging with a gastrointestinal motility monitor system. | Biased ligand (towards sig. prot.) | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Altarifi AA, David B, Muchhala KH, Blough BE, Akbarali H, Negus SS | 31:730-739 | |
| 93198 | A | Opioid receptors | OPRM | μ | Rat | OLICERIDINE | g protein | opioid analgesia and side effects | side effects of opioids | Acute TRV130 treatment produced robust antinociception, complete inhibition of gastrointestinal functionm and weak-abuse-related effects. | Biased ligand might induce physical dependence and addiction which was measured in intracranial self stimulation studies. | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Altarifi AA, David B, Muchhala KH, Blough BE, Akbarali H, Negus SS | 31:730-739 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | g protein | Analgesia/pain | opioid related adverse effects | TRV130 may offer analgesia withreduced risk of opioid‐induced nausea and vomitingcompared to current opioid analgesics | analgesia with reduced risk of opioid-induced nausea and vomiting | Biased ligand (towards sig. prot.) | Humans | Open-ended questions (report of AEs) | Soergel DG, Subach RA, Sadler B, Connell J, Marion AS, Cowan CL, Violin JD, Lark MW | 54:351-7 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | g protein | Analgesia/pain | antinociception/analgesia | PZM21 exhibited antinociceptive efficacy, without rewarding or reinforcing properties | antinociception with supraspinal and spinal component | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Kudla L, Bugno R, Skupio U, Wiktorowska L, Solecki W, Wojtas A, Golembiowska K, Zador F, Benyhe S, Buda S, Makuch W, Przewlocka B, Bojarski AJ, Przewlocki R | 176:4434-4445 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | β-arrestin | Analgesia/pain | rewarding effects and reinforcement | PZM21 exhibited antinociceptive efficacy, without rewarding or reinforcing properties | the ligand does not induce conditioned place preference | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Kudla L, Bugno R, Skupio U, Wiktorowska L, Solecki W, Wojtas A, Golembiowska K, Zador F, Benyhe S, Buda S, Makuch W, Przewlocka B, Bojarski AJ, Przewlocki R | 176:4434-4445 | |
| 3246 | A | Opioid receptors | OPRM | μ | Rat | PZM21 | β-arrestin | Analgesia/pain | rewarding effects and reinforcement | PZM21 exhibited antinociceptive efficacy, without rewarding or reinforcing properties | the ligand did not induce drug seeking behavior after abstinence period and no readily self-administration | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Kudla L, Bugno R, Skupio U, Wiktorowska L, Solecki W, Wojtas A, Golembiowska K, Zador F, Benyhe S, Buda S, Makuch W, Przewlocka B, Bojarski AJ, Przewlocki R | 176:4434-4445 | |
| A | Opioid receptors | OPRM | μ | Mouse | - | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | respiratory suppression | Direct correlation of increasing bias factor with an improved separation of therapeutic benefit from respiratory side effects | less respiratory suppression in G protein biased ligands | Biased ligand (towards sig. prot.) | Animals | Physical examination | Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, Cameron MD, Bannister TD, Bohn LM | 171:1165-1175.e13 | ||
| A | Opioid receptors | OPRM | μ | Mouse | - | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | respiratory suppression | Direct correlation of increasing bias factor with an improved separation of therapeutic benefit from respiratory side effects | robust respiratory suppression at lower doses of β-arrestin2-biased ligands | Biased ligand (towards sig. prot.) | Animals | Physical examination | Schmid CL, Kennedy NM, Ross NC, Lovell KM, Yue Z, Morgenweck J, Cameron MD, Bannister TD, Bohn LM | 171:1165-1175.e13 | ||
| 2594 | A | Opioid receptors | OPRM | μ | Mouse | morphine | gi/o-family | Analgesia/pain | antinociception/analgesia | Inhibition of β-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine | analgesia was prolonged and potentiated in β-arrestin 2 knock out mice | Knock out of sig. prot. | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT | 286:2495-8 | |
| 170847 | A | Opioid receptors | OPRM | μ | Mouse | CHEMBL4452384 | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | tolerance | SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented | SR-17080 showed no tolerance development at 24 mg/kg/day and slight decrease in potency at 48mg/kg/day in male mice; no tolerance development in female mice | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM | 45:416-425 | |
| 170847 | A | Opioid receptors | OPRM | μ | Mouse | CHEMBL4452384 | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | desensitization | SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented | G protein signaling was intact in SR-17018 treated mice in contrary to morphine treated mice | Biased ligand (towards sig. prot.) | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM | 45:416-425 | |
| 170847 | A | Opioid receptors | OPRM | μ | Mouse | CHEMBL4452384 | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | tolerance | SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented | restoration of morphine tolerance after three days of ligand treatment, which was also established with vehicle treatment | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM | 45:416-425 | |
| 170847 | A | Opioid receptors | OPRM | μ | Mouse | CHEMBL4452384 | g protein | Analgesia/pain | resensitization | SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented | restoration of morphine tolerance after three days of ligand treatment, which was also established with vehicle treatment | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM | 45:416-425 | |
| 170847 | A | Opioid receptors | OPRM | μ | Mouse | CHEMBL4452384 | g protein | Analgesia/pain | prevention of withdrawal | SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented | reduction of withdrawal signs under SR-17018 treatment, similar to buprenorphine | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Grim TW, Schmid CL, Stahl EL, Pantouli F, Ho JH, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM | 45:416-425 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | gi/o-family | Analgesia/pain | antinociception/analgesia | TRV130 may provide effective, rapid analgesia with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine | TRV130 produced statistically significant reduction in pain relative to placebo over 24 hours that was similar to that of morphine; analgesia occurred more rapidly with TRV130 at 5- and 30-minute time points | Biased ligand (towards sig. prot.) | Humans | Numeric rating scales (pain intensity, etc.) | Singla N, Minkowitz HS, Soergel DG, Burt DA, Subach RA, Salamea MY, Fossler MJ, Skobieranda F | 10:2413-2424 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | β-arrestin | Analgesia/pain | nausea and emesis | TRV130 may provide effective, rapid analgesia with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine | lower percentages of patients treated with TRV130 experienced nausea and vomiting than patients receiving morphine | Biased ligand (towards sig. prot.) | Humans | Physical examination | Singla N, Minkowitz HS, Soergel DG, Burt DA, Subach RA, Salamea MY, Fossler MJ, Skobieranda F | 10:2413-2424 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | β-arrestin | Analgesia/pain | respiratory suppression | TRV130 may provide effective, rapid analgesia with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine | lower percentages of patients treated with TRV130 experienced respiratory effects than patients receiving morphine | Biased ligand (towards sig. prot.) | Humans | Physical examination | Singla N, Minkowitz HS, Soergel DG, Burt DA, Subach RA, Salamea MY, Fossler MJ, Skobieranda F | 10:2413-2424 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | gi/o-family | Analgesia/pain | antinociception/analgesia | TRV130 may be associated with a lower incidence of AEs at dosing regimens associated with comparable analgesia. | Oliceridine 0,35- and 0,5mg demand dose regimens were consistently superior to placebo and equi-analgesic to morphine (1mg) | Biased ligand (towards sig. prot.) | Humans | Numeric rating scales (pain intensity, etc.) | Singla NK, Skobieranda F, Soergel DG, Salamea M, Burt DA, Demitrack MA, Viscusi ER | 19:715-731 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | β-arrestin | Analgesia/pain | respiratory suppression | TRV130 may be associated with a lower incidence of AEs at dosing regimens associated with comparable analgesia. | Oliceridine 0,35mg regimen showed a favorable safety and tolerability profile regarding respiratory adverse events compared to morphine (gatekeeping statistical approach) | Biased ligand (towards sig. prot.) | Humans | Physical examination | Singla NK, Skobieranda F, Soergel DG, Salamea M, Burt DA, Demitrack MA, Viscusi ER | 19:715-731 | |
| 93198 | A | Opioid receptors | OPRM | μ | Human | OLICERIDINE | β-arrestin | Analgesia/pain | GI dysfunction; constipation | TRV130 may be associated with a lower incidence of AEs at dosing regimens associated with comparable analgesia. | Oliceridine 0,35mg regimen showed a favorable safety and tolerability profile regarding gastrointestinal adverse events compared to morphine (gatekeeping statistical approach) | Biased ligand (towards sig. prot.) | Humans | Physical examination | Singla NK, Skobieranda F, Soergel DG, Salamea M, Burt DA, Demitrack MA, Viscusi ER | 19:715-731 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | gi/o-family | Analgesia/pain | respiratory suppression | PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist | dose-dependent respiratory depression that was maintained over the 60 min period following drug administration | Biased ligand (towards sig. prot.) | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G | 175:2653-2661 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | gi/o-family | Analgesia/pain | tolerance | PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist | development of tolerance to the antinociceptive effects | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G | 175:2653-2661 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | respiratory suppression | PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist | dose-dependent respiratory depression that was maintained over the 60 min period following drug administration | Biased ligand (towards sig. prot.) | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G | 175:2653-2661 | |
| 3246 | A | Opioid receptors | OPRM | μ | Mouse | PZM21 | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | tolerance | PZM21 depresses respiration in a manner similar to morphine, the classical opioid receptor agonist | development of tolerance to the antinociceptive effects | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G | 175:2653-2661 | |
| 2313 | A | Opioid receptors | OPRM | μ | Mouse | levorphanol | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | respiratory suppression | Levorphanol was a G-protein biased agonist at µ opioid receptor splice variants, consistent with diminished respiratory depressant activity, and displayed incomplete cross tolerance to morphine and oxycodone | Levorphanol decreased respiratory rate, however, the area under the curve was not significantly different from saline treated mice | Biased ligand (towards sig. prot.) | Animals | Physical examination | Le Rouzic V, Narayan A, Hunkle A, Marrone GF, Lu Z, Majumdar S, Xu J, Pan YX, Pasternak GW | 128:365-373 | |
| 93198 | A | Opioid receptors | OPRM | μ | Rat | OLICERIDINE | g protein | Analgesia/pain | antinociception/analgesia | The G-protein biased mu-opioid agonist, TRV130, produces reinforcing and antinociceptive effects | ED50 values for oxycodone and TRV130 were not significantly different | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Austin Zamarripa C, Edwards SR, Qureshi HN, Yi JN, Blough BE, Freeman KB | 192:158-162 | |
| 93198 | A | Opioid receptors | OPRM | μ | Rat | OLICERIDINE | g protein | Analgesia/pain | rewarding effects and reinforcement | The G-protein biased mu-opioid agonist, TRV130, produces reinforcing and antinociceptive effects | TRV130 and oxycodone showed the same potency as a reinforcer | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Austin Zamarripa C, Edwards SR, Qureshi HN, Yi JN, Blough BE, Freeman KB | 192:158-162 | |
| 3168 | A | Opioid receptors | OPRK | κ | Mouse | probe 1.1 [PMID: 24187130] | gi/o-family | Analgesia/pain | antinociception/analgesia | Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria | antinociception | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM | 9:ra117 | |
| 3168 | A | Opioid receptors | OPRK | κ | Mouse | probe 1.1 [PMID: 24187130] | g protein | Analgesia/pain | antipruritic | Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria | suppression of scratching behaviors | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM | 9:ra117 | |
| 3168 | A | Opioid receptors | OPRK | κ | Mouse | probe 1.1 [PMID: 24187130] | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | sedation | Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria | no suppression of ambulation compared to other agonists | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM | 9:ra117 | |
| 3168 | A | Opioid receptors | OPRK | κ | Mouse | probe 1.1 [PMID: 24187130] | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | sedation | Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria | no decrease in dopaminergic transmission | Biased ligand (towards sig. prot.) | Animals | measurement of electrophysiology | Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM | 9:ra117 | |
| 3168 | A | Opioid receptors | OPRK | κ | Mouse | probe 1.1 [PMID: 24187130] | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | sedation | Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria | no decrease in dopaminergic transmission | Biased ligand (towards sig. prot.) | Animals | instrument based examination of living organism | Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM | 9:ra117 | |
| 3168 | A | Opioid receptors | OPRK | κ | Rat | probe 1.1 [PMID: 24187130] | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | dysphoria | Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria | the ligand did not alter intracranial self-stimulation when compared to baseline or vehicle | Biased ligand (towards sig. prot.) | Animals | instrument based examination of living organism | Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM | 9:ra117 | |
| 3168 | A | Opioid receptors | OPRK | κ | Rat | probe 1.1 [PMID: 24187130] | β-arrestin-2 (non-visual arrestin-3) | Analgesia/pain | dysphoria | Triazole 1.1 retained the antinociceptive and antipruritic efficacies without inducing sedation or reductions in dopamine release, nor did it produce dysphoria | administration of the ligand suppressed the effect of lactic acid compared to vehicle administration | Biased ligand (towards sig. prot.) | Animals | instrument based examination of living organism | Brust TF, Morgenweck J, Kim SA, Rose JH, Locke JL, Schmid CL, Zhou L, Stahl EL, Cameron MD, Scarry SM, Aube J, Jones SR, Martin TJ, Bohn LM | 9:ra117 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) induce EGFR internalazation | Biased ligand (towards sig. prot.) | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) induce EGFR transactivation and ERK activation | Biased ligand (towards sig. prot.) | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) significantly increased ERK activation in mouse heart | Biased ligand (towards sig. prot.) | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | β1ARs without C-tail phosphorylation sites prevent EGFR transactivation | Knock in - mutant receptor with impared signalling | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | siRNS targeting β-arr1, β-arr2 or both significantly blocked ERK activation | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 370 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) induce EGFR internalazation | Biased ligand (towards sig. prot.) | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 370 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) induce EGFR transactivation and ERK1/2 activation | Biased ligand (towards sig. prot.) | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 370 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) significantly increased ERK activation in mouse heart | Biased ligand (towards sig. prot.) | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 370 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | β1ARs without C-tail phosphorylation sites prevent EGFR transactivation | Knock in - mutant receptor with impared signalling | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 370 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | siRNS targeting β-arr1, β-arr2 or both significantly blocked ERK activation | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 | |
| 1454 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | dobutamine | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | β1ARs without C-tail phosphorylation sites prevent EGFR transactivation and internalization plus leads to only minimal ERK activation | Knock in - mutant receptor with impared signalling | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 1454 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | dobutamine | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | Robust membrane translocation of GFP-β-arr | Tagged sig. prot | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 1454 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | dobutamine | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | siRNS targeting β-arr1, β-arr2 or both significantly blocked EGFR transactivation and associated ERK activation | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 1454 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | dobutamine | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | siRNA targeting of β-arrestin1/2 blocked EGFR internalization | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | siRNA targeting of β-arrestin1/2 blocked EGFR internalization | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 1454 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | dobutamine | β-arrestin-2 | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | ERK activation was completely blocked in the β-arrestin2–knockout mice | Knock out of sig. prot. | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | Cardiac contractility was significantly enhanced indicating a state of diminished βAR desensitization | Knock in - mutant receptor with impared signalling | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | βAR density reduced in WT after chronic agonist treatment but not in mutant. | Knock in - mutant receptor with impared signalling | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | Significant deterioration in cardiac function with marked LV dilatation and reduced fractional shortening | Knock in - mutant receptor with impared signalling | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | Increased interstitial fibrosis and apoptotic nuclei | Knock in - mutant receptor with impared signalling | Animals | Histological examination | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | Biased ligand failed to block reconsolidation of object recognition memory (ORM) whereas β1AR selective antagonists completely suppressed the ORM reconsolidation | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | Biased ligand suppressed memory reactivation-induced cAMP levels | Biased ligand (towards sig. prot.) | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | Biased ligand did not affect memory reactivation-induced ERK levels | Biased ligand (towards sig. prot.) | Animals | Histological examination | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 370 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | alprenolol | β-arrestin | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | Biased ligand failed to block reconsolidation of object recognition memory (ORM) | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin-2 | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | β-arrestin 2 played a key role in ORM reconsolidation whereas biased ligand failed to restore ORM reconsolidation in β-arrestin 2 knock out mice | Knock out of sig. prot. | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 3187 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | (-)-propranolol | β-arrestin-2 | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | Ablation of β-arrestin 2 or antagonist treatment abolished memory re-activation induced ERK activation | Knock out of sig. prot. | Animals | Histological examination | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 622 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | betaxolol | β-arrestin-2 | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | Ablation of β-arrestin 2 or antagonist treatment abolished memory re-activation induced de novo protein synthesis | Knock out of sig. prot. | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin-2 | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | Rescued β-arrestin 2 expression in knock-out mice restored pERK levels post memory reactivation | Knock out of sig. prot. | Animals | Histological examination | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 622 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | betaxolol | β-arrestin-2 | Psychiatric disorder | Memory retention | β1AR mediated β-arrestin signalling plays an important role in memory reconsolidation | Rescued β-arrestin 2 expression in knock-out mice restored ORM reconsolidation | Knock out of sig. prot. | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin-2 | Psychiatric disorder | Memory retention | Pharmalogical disruption of memory reconsolidation could help in treating drug addiction | Biased ligand increased re-activation of cocaine-induced conditioned place preference (CPP) memory compared to antagonist | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 803 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | carvedilol | β-arrestin-2 | Psychiatric disorder | Memory retention | Pharmalogical disruption of memory reconsolidation could help in treating drug addiction | Biased ligand increased re-activation of freezing behaviour in contextual fear memory test as compared to antagonist | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 370 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | alprenolol | β-arrestin-2 | Psychiatric disorder | Memory retention | Pharmalogical disruption of memory reconsolidation could help in treating fear-related disorders | Biased ligand increased re-activation of freezing behaviour in contextual fear memory test as compared to antagonist | Biased ligand (towards sig. prot.) | Animals | Observation of animal behavior (HTR, hot plate, tail-flick, etc.) | Liu X, Ma L, Li HH, Huang B, Li YX, Tao YZ, Ma L | 112:4483-8 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | cardioprotection | Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity | significant deterioration in cardiac function | Knock in - mutant receptor with impared signalling | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | cardioprotection | Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity | marked LV dilatation | Knock in - mutant receptor with impared signalling | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | cardioprotection | Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity | reduced fractional shortening | Knock in - mutant receptor with impared signalling | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | cardioprotection | Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity | increased interstitial fibrosis | Knock in - mutant receptor with impared signalling | Animals | Histological examination | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| 2091 | A | Adrenoceptors | ADRB1 | β1-adrenoceptor | Mouse | isoprenaline | β-arrestin | Heart disease | cardioprotection | Activation of this β1AR/EGFR transactivation pathway provides cardioprotection in vivo under conditions of catecholamine toxicity | increased apoptotic nuclei | Knock in - mutant receptor with impared signalling | Animals | Histological examination | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 | |
| A | Lysophospholipid (S1P) receptors | S1PR5 | S1P5 | Mouse | - | β-arrestin-2 (non-visual arrestin-3) | Vascular disease | atherosclerosis | β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. | less atherosclerosis in β-arrestin2-deficient mice | Knock out of sig. prot. | Animals | Histological examination | Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ | 103:70-9 | ||
| A | Lysophospholipid (S1P) receptors | S1PR5 | S1P5 | Mouse | - | β-arrestin-1 (non-visual arrestin-2) | Vascular disease | prevention hyperplasia | β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. | attenuation of neointimal hyperplasia | Knock out of sig. prot. | Animals | Histological examination | Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ | 103:70-9 | ||
| A | Lysophospholipid (S1P) receptors | S1PR5 | S1P5 | Mouse | - | β-arrestin-2 (non-visual arrestin-3) | Vascular disease | hyperplasia | β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. | exacerbation of neointimal hyperplasia | Knock out of sig. prot. | Animals | Histological examination | Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ | 103:70-9 | ||
| A | Lysophospholipid (S1P) receptors | S1PR5 | S1P5 | Mouse | - | β-arrestin-1 (non-visual arrestin-2) | Vascular disease | antiproliferative | β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. | augmented medial small muscle cell proliferation in β-arrestin1-knock out mice | Knock out of sig. prot. | Animals | Histological examination | Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ | 103:70-9 | ||
| A | Lysophospholipid (S1P) receptors | S1PR5 | S1P5 | Mouse | - | β-arrestin-2 (non-visual arrestin-3) | Vascular disease | proliferation | β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. | reduced medial small muscle cell proliferation in β-arrestin2-knock out mice | Knock out of sig. prot. | Animals | Histological examination | Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ | 103:70-9 | ||
| A | Lysophospholipid (S1P) receptors | S1PR5 | S1P5 | Mouse | - | β-arrestin-1 (non-visual arrestin-2) | Vascular disease | apoptosis | β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. | reduced small muscle cell apoptosis in β-arrestin1-knock out mice | Knock out of sig. prot. | Animals | Histological examination | Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ | 103:70-9 | ||
| A | Lysophospholipid (S1P) receptors | S1PR5 | S1P5 | Mouse | - | β-arrestin-2 (non-visual arrestin-3) | Vascular disease | antiapoptotic effect | β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration and these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. | augmented small muscle cell apoptosis in β-arrestin2-knock out mice | Knock out of sig. prot. | Animals | Histological examination | Kim J, Zhang L, Peppel K, Wu JH, Zidar DA, Brian L, DeWire SM, Exum ST, Lefkowitz RJ, Freedman NJ | 103:70-9 | ||
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