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-androstane3a,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. Cats were anaesthetized with a mixture of chloralose (70 mg/kg) and sodium pentobarbitone (12 mg/kg) injected intraperitoneally; rabbits and dogs were anaesthetized with sodium pentobarbitone (45 mg/kg) injected intravenously, and hens with sodium barbitone (200 mg/kg) injected intravenously. In all species the trachea was intubated and artificial ventilation applied throughout each experiment Twitches and tetani of a gastrocnemius muscle were elicited by stimulating the peripheral portion of the crushed sciatic nerve in the popliteal space with rectangular shocks of

Pre- and Postsynaptic Mechanisms Involved in Tetanic Fade Induced by Pancuronium in the Isolated Rat Muscle

“…Thus, in view of the classic pharmacolo gy of pancuronium [13][14][15][16], a postsynaptic blocking mechanism of the competitive type, it is obviously the most probable explanation for the decrease in e.p.ps quantal size induced by this compound. Although theoretically a postsynaptic action as the block of the 'open' end-plate channel could also explain that finding, it has been previously demonstrated that in the presence of pancuronium such a blockade occurs seldom and only under very hyperpolarized membrane potentials [17], Thus, it is likely that a classic postsynaptic competitive blocking action was the only mechanism underlying the decrease in e.p.ps quantal size induced by pancuronium.…”

Sympathomimetic Effects of Pancuronium Bromide on the Cardiovascular System of the Pithed Rat: A Comparison With the Effects of Drugs Blocking the Neuronal Uptake of Noradrenaline

“…Pancuronium bromide is a steroid non-depolarizing neuromuscular blocking agent (Buckett, Marjoribanks, Marwick & Morton, 1968). In clinical use pancuronium can produce cardiovascular stimulation, part of which has been explained by a vagolytic action (Saxena & Bonta, 1970;Hughes & Chapple, 1976).…”

Anaphylaxis to thiopentone: A case report

“…Pancuronium originally showed no evidence of causing histamine release in man and laboratory animals. 13 Recently, severe bronchospasm after pancuronium 14-17 has been reported. Profound hypotension was not a feature of these cases.…”