Effect of morphine antagonists on drug-induced hypothermia in mice and rats

Since it has been reported that the narcotic antagonist analgesic, cyclazocine, has thymoleptic activity in man, certain neuropharmacological properties of this compound have been retrospectively analysed in rodents using diprenorphine, naloxone and RX 336-X 336-M (7,8-dihydro-5',6'-dimethylcyclohex-5'-eno 1',2',8',14 codeinone) as reference narcotic antagonists and morphine, desmethylimipramine and d-amphetamine as standard psychotropic agents. From interactional studies with alpha-methylparatyrosine (alpha-MT) in rats, and apomorphine, oxotremorine or reserpine in mice, the calorigenic activities of each compound were compared. Diprenorphine, naloxone and morphine (each at doses ranging from 1-30 mg/kg, s.c.) had no significant calorigenic effect in any test. Evidence of potential antidepressant activity for cyclazocine was based on a high dose (30 mg/kg, s.c.) preventing the development of reserpine-induced hypothermia. RX 336-M (0.5-16 mg/kg, s.c.) reversed established hypothermia in the reserpine and alpha-MT tests. Since this calorigenic action was not antagonised by naloxone it was concluded that narcotic receptors were probably not involved in the mediation of the effect. Although RX 336-M resembled desmethylimipramine and d-amphetamine in the reserpine (reversal) and apomorphine tests, contrasting data from the reserpine (prevention), oxotremorine and alpha-MT tests indicated possible psychotropic activity based on different neurochemical mechanisms.