The effects of ethanol alone and in combination with phenobarbital, chlorpromazine, or chlordiazepoxide

Abstract

The nature of the interaction of ethanol (E) in combination with phenobarbital (Pb), chlorpromazine (CPZ), or chlordiazepoxide (CDP) was investigated in our laboratory. E, Pb, CPZ, or CDP was administered ip to male, albino mice and the dose causing 50% of the mice to fall from a 60° inclined screen (median paralyzing dose, PD50) determined for each agent. Since the dose-response curves did not deviate from parallelism ( P > 0.05), one-half the PD50 of E was then given in combination with one-half the PD50 of Pb, CPZ, or CDP such that the times of peak effect coincided. Only CDP in combination with E produced a potentiation of effects in this test method: Pb and CPZ in combination with E resulted in addition of effects. In a similar manner, one-half the PD50 of Pb, CPZ, or CDP was combined with one-half the loss of righting reflex ED50 of E. In this testing procedure, all three agents in combination with E demonstrated potentiation. Blood levels of ethanol (BLE) were followed in both of the above studies to determine the possibility that increased BLE might be responsible for the potentiation seen. Blood sample times were 5, 15, 30, 60, and 120 min post E administration. Combinations of drug with E were compared to identical doses of E administered in the absence of a drug. In no case was a significant increase in BLE seen at the early collection periods, a time by which the behavioral effects would have already occurred. Therefore, elevations in BLE cannot account for the behavioral effects seen. However, our data do suggest that CPZ in combination with one-half the PD50 of E may retard the rate of disappearance of E from the blood.