Studies of the possible role of brain endorphins in pentobarbital anesthesia and toxicity in mice.

In an attempt to ascertain whether opiate receptors and brain enkephalins or endorphins are involved in pentobarbital anesthesia and toxicity, the effects of 1) two pure narcotic antagonists, naloxone and naltrexone, 2) morphine sulfate, 3) D-phenylalanine, an inhibitor of carboxypeptidase A, and 4) D-leucine, an inhibitor of leucineaminopeptidase, in combination with D-phenylalanine, were studied in mice. Both naloxone and naltrexone, (1, 5 and 10 mg/kg) administered subcutaneously to mice were unable to modify the duration of anesthesia when they were injected 5 min prior to a challenge dose (75 mg/kg) of pentobarbital (ip). The onset of anesthesia was unaltered by naloxone (1, 5 and 10 mg/kg) and naltrexone (1 mg/kg). Higher doses of naltrexone (5 and 10 mg/kg) delayed the onset of anesthesia slightly. Morphine (1, 2.5 and 5 mg/kg) given 30 min before pentobarbital did not modify the onset or the duration of anesthesia. D-Phenylalanine (250 mg/kg), and D-phenylalanine + D-leucine (250 mg/kg each) injected ip an hour before pentobarbital did not affect either onset or duration of anesthesia. Naltrexone (10 mg/kg, ip) given 5 min before pentobarbital did not alter the LD50 of the latter. The studies do not support a role of enkephalins or endorphins in pentobarbital anesthesia or toxicity, and suggest a need for caution in using narcotic antagonists in treating pentobarbital toxicity.