The effect of phenobarbitone pretreatment on the narcotic antagonistic potency of naloxone in mice.

Pretreatment with phenobarbitone (5.0-20.0 mg/kg, s.c.) did not alter the antinociceptive effect (tail-flick assay) of morphine measured 4.5 h later. However, naloxone was more potent in antagonising this antinociceptive effect in phenobarbitone-pretreated mice than in saline-retreated animals. Concomitant administration of naloxone in the pretreatment regime did not alter the effect of phenobarbitone. The enhanced naloxone potency was related to the amount of phenobarbitone given, and was observable at 3.0 and 4.5 h after pretreatment. It was no longer apparent at 6.0 h. Because of a difference in time course and in the ability of naloxone to block the phenomenon, it is suggested that the mechanisms underlying the increase in naloxone potency induced by phenobarbitone pretreatment and morphine pretreatment may not be the same.