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Vol. 296, Issue 3, 939-946, March 2001
-Opioid Agonists in Rhesus Monkeys:
Effects on Chemically Induced Thermal Hypersensitivity
Alcohol and Drug Abuse Research Center, Harvard Medical
School-McLean Hospital, Belmont, Massachusetts (M.R.B., N.K.M.,
S.S.N.); and the Laboratory of Medicinal Chemistry, National Institute
of Diabetics, Digestive and Kidney Diseases and National Institute of
Health, Bethesda, Maryland (M.S.F., K.C.R.)
The effects of SNC80 and other structurally related 
-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 the
T10 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 the
T10, and 10.0 mg/kg SNC80 fully blocked the
effects of capsaicin. The -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 -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 -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.
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