Effect of naloxone on antinociceptive activity of phenoxybenzamine.

Phenoxybenzamine was found to have antinociceptive activity in the mouse writhing syndrome test. The percent protection against writhing was dose related from 2.0 to 164.6 μM/kg phenoxybenzamine (ED-50, 37.1 ± 2.0 μM/kg). The dose-response curve for phenoxybenzamine was shifted to the left when morphine was administered. Administration of morphine, 1.12 μM/kg, reduced the ED-50 for phenoxybenzamine to 4.5 ± 1.3 μM/kg. Administration of naloxone shifted the dose response curve for phenoxybenzamine to the right. Naloxone 0.03 μM/kg increased the ED-50 for phenoxybenzamine to 102.5 ± 22.7 μM/kg. Chronic treatment with phenoxybenzamine did not change the antinociceptive response to phenoxybenzamine. The α-adrenergic blockers, phenotolamine and tolazoline showed weak antinociceptive activity which was not blocked by naloxone.