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
1The aminosteroid Org. NA 13 (3ai-dimethylamino-5i-androstan-2,3-ol-I7-one) was shown to be a more potent local anaesthetic than lignocaine in rats and guinea-pigs. 2 Experimental arrhythmias induced in mice by chloroform, in rats by aconitine and in dogs by coronary artery ligation were corrected by Org. NA 13 at doses from 10 to 50 mg/kg intravenously. 3 In contrast to lignocaine, other local anaesthetics and ,B-adrenoceptor blocking drugs, Org. NA 13 did not show any activity against the arrhythmias induced by ouabain in dogs. 4 The acute toxicity in whole animals and myocardial toxicity in the rabbit isolated atrium appeared to be less than that observed with lignocaine.
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