RT Journal Article
SR Electronic
T1 Antinociceptive Effects of δ-Opioid Agonists in Rhesus Monkeys: Effects on Chemically Induced Thermal Hypersensitivity
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 939
OP 946
VO 296
IS 3
A1 Michael R. Brandt
A1 M. Scott Furness
A1 Nancy K. Mello
A1 Kenner C. Rice
A1 S. Stevens Negus
YR 2001
UL http://jpet.aspetjournals.org/content/296/3/939.abstract
AB The effects of SNC80 and other structurally related δ-opioid receptor agonists were assessed under conditions of chemically induced hypersensitivity to thermal stimuli in four rhesus monkeys. The shaved tail of each monkey was exposed to warm water (38, 42, 46, and 50°C), and the tail-withdrawal latency from each temperature was recorded. The effects of drugs on the temperature that produced a 10-s tail-withdrawal latency (the T10 value) were examined. Capsaicin (0.01–0.32 mg) injected into the tail of monkeys dose dependently decreased the T10, indicating that capsaicin increased sensitivity to thermal stimuli. A dose of 0.1 mg of capsaicin decreased theT10 from 48.0 to 42.1°C (a −5.9°C change) 15 min after injection. SNC80 (1.0–10.0 mg/kg s.c.) dose dependently blocked the capsaicin-induced decrease in theT10, and 10.0 mg/kg SNC80 fully blocked the effects of capsaicin. The δ-selective antagonist naltrindole (0.1–1.0 mg/kg) dose dependently antagonized the effects of SNC80, whereas a μ-selective dose of the opioid antagonist quadazocine (0.1 mg/kg) did not. Two other δ-selective agonists, SNC162 (1.0–10.0 mg/kg) and SNC243A (1.0–10.0 mg/kg), also dose dependently blocked capsaicin-induced thermal hypersensitivity. In contrast, neither SNC67 (10.0 mg/kg), which is the (−)-enantiomer of SNC80, nor the nonsteroidal anti-inflammatory drug (NSAID) ketorolac (1.0–10.0 mg/kg) modified the effects of capsaicin. SNC80 was also effective in reversing thermal hypersensitivity induced by prostaglandin E2 (0.0158 mg) and Freund's complete adjuvant (10% concentration). These findings suggest that δ-agonists have antinociceptive effects in primates under conditions of chemically induced thermal hypersensitivity and might be effective under a broader range of conditions than clinically available NSAIDs. The American Society for Pharmacology and Experimental Therapeutics