A Comparison of the Antinociceptive and Adverse Effects of the μ‐Opioid Agonist Morphine and the δ‐Opioid Agonist SNC80

: δ‐Opioid receptor agonists have been postulated to induce analgesia without the adverse effects commonly associated with μ‐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 PCO2 were observed with the higher doses of SNC80 (≥40 mg/kg). In conclusion, the δ‐opioid agonist SNC80 lacks both the analgesic efficacy and adverse effects of μ‐opioids. However, the activity of SNC80 in the inflammatory model suggests δ‐opioid agonists may be useful analgesics in the treatment of some forms of inflammatory pain.