AUGMENTATION OF OPIOID-INDUCED ANTINOCICEPTION BY THE ATYPICAL ANTIPSYCHOTIC DRUG RISPERIDONE IN MICE

Risperidone is a novel atypical neuroleptic with a favorable profile o f side effects due to its unique pharmacological activity: it exhibits both potent dopamine D-2 and 5-HT2 receptor blocking activity, as wel l as high affinity for alpha(1) and alpha(2) adrenergic receptors and histamine H-1 receptor. We found that risperidone has a potent antinoc iceptive effect in the tailflick assay with an ED50 of 26.4 mg/kg. Thi s effect of risperidone was antagonized by naloxone (P < 0.05). This s ensitivity to naloxone indicates that at least some of the analgesic e ffects of risperidone are mediated by an opioid mechanism of action. b eta-FNA (mu(1) mu(2)-antagonist), naloxonazine (mu 1-antagonist) and n orbinaltorphamine (nor-BNI; kappa(1)-analgesia) reversed risperidone a ntinociceptive effect (P < 0.05). Naltrindole (delta-antagonist) only partially reversed risperidone antinociceptive effect. We found that t he sensitivity of risperidone antinociceptive effect to selective anta gonists implies involvement of mu(1)-, delta(2)- and kappa(1)-opioid a nd to a lesser extent delta-opioid mechanisms. These results suggest a possible role for risperidone both in the management of pain and in t he management of opiate withdrawal and detoxification. (C) 1997 Elsevi er Science Ireland Ltd.