delta-Opioid receptor agonists have been postulated to induce
analgesia without the adverse effects commonly associated with mu-
opioids e.g.
morphine. In the present study, we evaluated the occurrence of antinociceptive and
opioid-like side effects in rats (n=5-7) treated with a single dose of subcutaneous
morphine (0.01 to 40 mg/kg) or
SNC80 (0.63 to 80 mg/kg). The antinociceptive effects of
morphine and
SNC80 were compared using a range of nociceptive tests including the tail withdrawal test, the
acetic acid-induced abdominal constriction (writhing) assay, the automated
formalin test and a model of
inflammation-induced
thermal hyperalgesia. The adverse effects of both drugs were examined in animal models for gastrointestinal (GI) inhibition (
charcoal test; ricinus oil test),
respiratory depression (blood-gas analysis), motor disturbances (automated rotarod model) and abuse liability (
drug discrimination learning).
Morphine displayed significant antinociceptive and adverse effects in all the animal models employed.
SNC80 exhibited a significant effect in the writhing test and limited efficacy in a model of
inflammation-induced thermal
hypersensitivity. A delay in the occurrence of diarrhoea and some limited increases in PCO(2) were observed with the higher doses of
SNC80 (> or =40 mg/kg). In conclusion, the delta-
opioid agonist
SNC80 lacks both the
analgesic efficacy and adverse effects of mu-
opioids. However, the activity of
SNC80 in the inflammatory model suggests delta-
opioid agonists may be useful
analgesics in the treatment of some forms of inflammatory
pain.