Hypothermia and poikilothermia induced by a kappa-agonist opioid and a neuroleptic.

When an opioid acting selectively at the kappa opioid receptor is administered subcutaneously to rats along with a neuroleptic at an ambient temperature of 20 degrees C a marked hypothermia ensues. The combination of U-50,488H (a kappa agonist) and chlorpromazine (a neuroleptic) caused a drop in body temperature amounting to as much as 11 degrees C, with all animals recovering after 24-48 h. Naloxone partially reversed the hypothermia. Similar, but less dramatic, decreases in body temperature occurred with other neuroleptics and weaker kappa agonists. The induction of poikilothermia was indicated when the body temperature approached the environment temperature and lethality resulted in 100% of the animals at ambient temperatures of 5 degrees C or 35 degrees C. The potential utility of this or similar combinations of drugs lies in such diverse applications as cardiac surgery, treatment of the near-drowning syndrome and space travel.