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Hemodynamic effects of GI 87084B, an ultra-short acting mu-opioid analgesic, in anesthetized dogs

MK James, A Vuong, MK Grizzle, SV Schuster and JE Shaffer

Department of Pharmacology, Glaxo Inc. Research Institute, Research Triangle Park, North Carolina.

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.

Volume 263, Issue 1, pp. 84-91, 10/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics.