Prolongation of anesthetic action by BNPP (bis-[p-nitrophenyl] phosphate)

Bis-[p-nitrophenyl] phosphate, BNPP, an enzyme inhibitor of the organophosphate class, has been used to inhibit the enzyme, carboxylic ester hydrolase EC 3.1.1.1. Esterases play a major role in the rapid metabolism of propanidid in vivo; in fact, the short duration of action of this intravenous anesthetic agent is due to this rapid hydrolysis. The duration of anesthesia with propanidid alone in healthy mongrel dogs was 10.1 +/- 2.1 (SEM) minutes. When the dogs were pretreated with BNPP, propanidid anesthesia time was prolonged to 38.2 +/- 7.9 (SEM) minutes. Measurements of serum propanidid concentration demonstrated that prolonged high levels of propanidid were associated with the extended anesthesia time. Therefore, BNPP can significantly alter the anesthetic action of propanidid by inhibition of the enzyme system responsible for the rapid hydrolysis of the agent. The experimental model used in the present study provides a means for investigation of effects of certain drugs when their metabolism is impaired.