Agonist-antagonistic interactions of pentazocine with morphine studied in mice

Interactions between the antinociceptive effects of pentazocine and morphine were studied in mice. In the tail-pressure test, the antinociceptive effect of pentazocine, 4.75 to 9.5 mg/kg, SC, was synergistic to that of morphine, 0.69 to 1.38 mg/kg, SC. In the acetic acid writhing test, the effect was also synergistic with pentazocine, 7.13 to 9.5 mg/kg, SC, and morphine, 1.03 to 1.38 mg/kg, SC. In the tail-pinch test, larger doses of morphine than those above were required to suppress the nociceptive response, and simultaneous administration of pentazocine, 2.38 to 19.0 mg/kg, SC, and morphine, 2.75 mg/kg, SC, produced antagonistic effects. Pentazocine, 19.0 mg/kg, completely antagonized the effect of morphine, 2.75 mg/kg, with simultaneous administration at these doses always nearly equipotent to administration of pentazocine alone. These results suggested that when pentazocine and morphine are simultaneously administered, pentazocine synergizes or antagonizes to antinociceptive effects of morphine depending on the dose sizes of morphine and pentazocine, and that the relative saturation levels of morphine and pentazocine at the receptor may be important factors in determining whether the interaction of pentazocine with morphine is antagonistic or synergistic.