The effects of
SNC80 and other structurally related
delta-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 degrees 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 T(10) value) were examined.
Capsaicin (0.01-0.32 mg) injected into the tail of monkeys dose dependently decreased the T(10), indicating that
capsaicin increased sensitivity to thermal stimuli. A dose of 0.1 mg of
capsaicin decreased the T(10) from 48.0 to 42.1 degrees C (a -5.9 degrees C change) 15 min after injection.
SNC80 (1.0-10.0 mg/kg s.c.) dose dependently blocked the
capsaicin-induced decrease in the T(10), and 10.0 mg/kg
SNC80 fully blocked the effects of
capsaicin. The delta-selective antagonist
naltrindole (0.1-1.0 mg/kg) dose dependently antagonized the effects of
SNC80, whereas a mu-selective dose of the
opioid antagonist quadazocine (0.1 mg/kg) did not. Two other delta-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 E(2) (0.0158 mg) and Freund's complete adjuvant (10% concentration). These findings suggest that delta-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.