Effects of the combination of tripelennamine and pentazocine at the behavioral and molecular levels.

The purpose of the present experiments was to determine if the antihistamine tripelennamine potentiates the morphine-like effects of the narcotic-antagonist analgesic pentazocine at the behavioral level or the molecular level or both. At the behavioral level, the effects of pentazocine were determined alone and in combination with tripelennamine in rats trained to discriminate between saline and either morphine or the psychotomimetic narcotic derivative SKF 10,047. The interaction between pentazocine and tripelennamine were also evaluated in the guinea-pig ileum preparation and in the [3H]-naloxone opiate receptor binding assay. Tripelennamine significantly enhanced the morphine-like discriminative stimulus effects of pentazocine and markedly reduced the SKF 10,047-like stimulus effects of pentazocine. Naloxone antagonized the morphine-like effects of pentazocine plus tripelennamine. Pentazocine significantly constricted pupils in the rat, an effect which was additive with the mydriatic effects of tripelennamine. Inhibition of the twitch-height of the electrically stimulated guinea-pig ileum by pentazocine was not affected by tripelennamine. Further, tripelennamine did not modify the Ke for naloxone in antagonizing pentazocine. Inhibition of specific [3H]-naloxone binding by pentazocine was also not affected by tripelennamine. These results are consistent with the hypothesis that the potentiation of the morphine-like effects of pentazocine by tripelennamine which was observed behaviorally was not due to molecular interactions at the morphine receptor. At least a part of this interaction may be attributable to tripelennamine decreasing the psychotomimetic actions of pentazocine.