title: Hemodynamic effects of GI 87084B, an ultra-short acting mu-opioid analgesic, in anesthetized dogs.
abstract: Hemodynamic effects of GI 87084B, a novel ultra-short acting mu-opioid agonist, were studied in anesthetized dogs. In these studies, GI 87084B (0.3-20 nmol/kg/min i.v.) produced dose-dependent decreases in heart rate, arterial blood pressure, +dP/dt and cardiac output. Alfentanil produced similar effects but was less potent. After termination of the infusions (397 nmol/kg cumulative dose), the hemodynamic effects of GI 87084B dissipated over 30 to 40 min. The effects of alfentanil, however, persisted throughout the 60-min recovery period. Infusion of GI 87084B at lower dose rates (0.001-0.3 nmol/kg/min) in barbiturate-anesthetized dogs showed a threshold dose of 0.1 to 0.3 nmol/kg/min for effects on hemodynamic variables. After infusing 0.3 nmol/kg/min of GI 87084B for 10 min, hemodynamic variables recovered rapidly (10-20 min). Boli of GI 87084B (0.3-100 nmol/kg i.v.) produced dose-dependent decreases in the same hemodynamic variables. The duration of these effects increased from 5 to 20 min at 3 nmol/kg to 15 to 45 min at 100 nmol/kg. Naloxone (0.063 mg/kg/hr) decreased the magnitude and duration of the effects of GI 87084B, suggesting that these effects are mediated through opioid receptors. In summary, GI 87084B produced hemodynamic effects consistent with mu-opioid agonism when administered by infusion or bolus, but these effects were brief in duration compared to other opioids.
authors.affiliation: Department of Pharmacology, Glaxo Inc. Research Institute, Research Triangle Park, North Carolina.
authors.forename: M K
authors.initials: MK
authors.lastname: James
authors.forename: A
authors.initials: A
authors.lastname: Vuong
authors.forename: M K
authors.initials: MK
authors.lastname: Grizzle
authors.forename: S V
authors.initials: SV
authors.lastname: Schuster
authors.forename: J E
authors.initials: JE
authors.lastname: Shaffer
mesh_terms: D015760:Alfentanil / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D000077208:Remifentanil
chemical_list: D000700:Analgesics; D010880:Piperidines; D015760:Alfentanil; D000077208:Remifentanil