Potentiation of pentazocine antinociception by tripelennamine in the rat.

The effect of tripelennamine on pentazocine antinociception in rats was investigated utilizing a low temperature (51.5 degrees C) hot-plate technique. Tripelennamine (10 and 20 mg/kg i.p.) showed some antinociceptive activity, which was not antagonized by naloxone. Pentazocine antinociception was potentiated by simultaneous administration of a large dose (20 mg/kg) but not a small dose (5 mg/kg) of tripelennamine. Potentiation was not observed when tripelennamine was administered 2 hr before the injection of pentazocine and chronic administration of tripelennamine for 14 days did not alter pentazocine antinociceptive activity. After administration of pentazocine and tripelennamine, levels of pentazocine under concentration-time curves in the brain and plasma were slightly and significantly larger, respectively, than the levels obtained by the administration of pentazocine alone. After the administration of tripelennamine and pentazocine, the brain tripelennamine concentration at 1/4 hr was about 2.6 times that after the administration of tripelennamine alone. The results suggest that the effect of tripelennamine on pentazocine antinociception is additive; very little was through a mechanism of inhibition of pentazocine metabolism.