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

1. Morphine pretreatment (8.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 4 h later, but enhanced by the antagonistic potency of naloxone. 2. Pretreatment with chlorpromazine hydrochloride (0.5 2.0 mg/kg s.c.) potentiated the antinociceptive effect of morphine measured 4.5 h later. The antagonistic effect of naloxone was also enhanced. 3. The observed effect of chlorpromazine on naloxone potency was augmented when naloxone hydrochloride 0.2 mg/kg was administered in the pretreatment regime. 4. The enhanced naloxone potency induced by morphine pretreatment was inhibited by chlorpromazine administered 0.5 hr before the morphine pretreatment. 5. These results indicate that pretreatment with either morphine or chlorpromazine increased the antagonistic potency of naloxone. However, it appears that these two drugs act by different mechanisms.