The mode of action of promethazine in potentiating narcotic drugs.

Evidence is presented from more than 300 subjects to show that promethazine potentiates the action of six different narcotics (morphine, pethidine, oxymorphone, hydromorphone, fentanyl and pentazocine). In each instance there was prolongation rather than deepening of the narcotic action. Such an effect is consistent with the known membrane-stabilizing action of promethazine and is likely to occur at the site of inactivation of the narcotic (e.g. liver) rather than at its principal site of action, the brain. In the light of these findings promethazine premedication should be reserved for situations where the use of intravenous anaesthetics is anticipated. At the same time promethazine may prove to be a useful drug in certain other situations where too rapid inactivation of the principal drug presents a therapeutic problem.