THE PHARMACOLOGY OF PANCURONIUM BROMIDE (ORG.NA97), A NEW POTENT STEROIDAL NEUROMUSCULAR BLOCKING AGENT

Abstract

The incorporation of a biologically active group into a naturally occurring structure is an interesting approach to new pharmacological agents. For example, when an acetylcholine-like structure is incorporated in ring-A of 5a-androstane-17-one or 5a-pregnan-20-one, neuromuscular blocking agents of up to one-fifteenth the potency of tubocurarine are obtained (Lewis, Martin-Smith, Muir & Ross, 1967). Although of limited clinical value, such compounds present useful leads for further chemical exploration, particularly the synthesis of bisquaternary amino-steroidal salts. A series of 2,8,16,3-diamino-5a-androstane-3a,17p-diol dimethohalide derivatives was described by Buckett, Hewett & Savage (1967). One of them, 2ft,16,/-dipiperidino-5a-androstane-3a,17,8-diol diacetate dimethobromide (code number Org.NA97; approved name pancuronium bromide), is a potent neuromuscular blocking agent and in the experiments described in this paper its actions were compared with those of tubocurarine chloride. OAc ",,MeI N Me Acd H 2Br-,H20 METHODS Nerve-muscle preparations