title: The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist.
abstract: The cardiovascular and central nervous system effects of the kappa opioid receptor agonist U-62066E were investigated in ten normal male subjects who received U-62066E or placebo with low or high dose naloxone in a randomized, double blind study. Blood pressure and heart rate in the supine and standing position, plasma adrenaline and noradrenaline, regional Doppler blood velocity indices and psychometric assessments were recorded for 1.25 h before and 6 h following injection. U-62066E caused sedation and dysphoria but no euphoria. Plasma noradrenaline was increased by U62066E when compared with basal levels. This action of U62066E was prevented by high but not low dose naloxone. U-62066E had no significant effect on blood pressure, heart rate or regional blood flow indices in the vessels studied and no effect on plasma adrenaline levels. Since U62066E at a dose known to have marked kappa effects was not found to influence cardiovascular indices our results do not support a major role for kappa opioids in the control of the circulation. However, U62066E may influence noradrenaline release or clearance and cause sedation and psychotomimetic effects.
authors.affiliation: Department of Therapeutics, Queen's Medical Centre, Nottingham, UK.
authors.forename: G H
authors.initials: GH
authors.lastname: Rimoy
authors.forename: D M
authors.initials: DM
authors.lastname: Wright
authors.forename: N K
authors.initials: NK
authors.lastname: Bhaskar
authors.forename: P C
authors.initials: PC
authors.lastname: Rubin
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D011594:Psychometrics; D011674:Pulse / Q000187:drug effects; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*
chemical_list: D002491:Central Nervous System Agents; D004232:Diuretics; D006993:Hypnotics and Sedatives; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C051272:spiradoline; D009638:Norepinephrine