Clinical investigation of a new phenothiazine compound, methdilazine

Abstract

The applicability of new phenothiazine compound, methdilazine, to the clinical practice of anesthesiology was examined in 527 adult patients. Methdilazine in a dose of 25 mg. by intramuscular injection, when combined with 50 mg. of meperidine, was found to be a useful drug for the preanesthetic preparation of the surgical patient. The patients who had received methdilazine were more drowsy after operation than those in the placebo group but could be readily aroused. The preanesthetic administration of the drug did not appear to offer any protection against postoperative emesis.The use of methdilazine in the prevention of postoperative emesis was studied follOWing the intramuscular injection of 12.5 mg. at the termination of anesthesia. There was a significant decrease in emetic symptoms in the 3 hour postoperative period. Postanesthetic drowsiness and hypotension were minimal. M ethdilazine was administered to patients during the first 24 hour postoperative period. These patients were given 50 mg. of meperidine whenever they requested an analgesic drug to relieve their pain. It was found that the patients who had received methdilazine had a significantly greater requirement for meperidine than those in the placebo group. It was concluded that methdilazine exhibited analgesic antagonism.

Harnessing the cyclization strategy for new drug discovery

“…14 , based on the antipsychotic drug chlorpromazine, many derivatives have been developed. Considering the flexibility of the side chain, cyclizing the terminal dimethylamino group in chlorpromazine may reduce the flexibility and give methdilazine and prochlorperazine with improved antiemetic effect 89 , 90 .

Figure 14 Drug discovery based on the chain cyclization.

…”