PHARMACOLOGY OF ORG-NC-45 COMPARED WITH OTHER NON-DEPOLARIZING NEUROMUSCULAR BLOCKING-DRUGS

From results of pharmacological tests on the neuromuscular and autonomic blocking actions of a series of pancuronium analogues, Org NC 45, the Cl 6 monoquatemary analogue of pancuronium, was selected for detailed study. Org NC 45 has a non-depolarizing mechanism of action, is more rapid in onset and shorter in duration of action than pancuronium. It shows less cumulation than pancuronium or tubocurarine, and is easily antagonized by anricholinesterases and aminopyridines. Org NC 45 exhibits a low propensity to release histamine. Its ability to inhibit cholinesterases is not likely to be important at neuromuscular blocking doses. Org NC 45 possesses negligible ganglion-blocking activity and there is a wide margin between neuromuscular and vagal blocking doses. Thus cardiovascular side-effects are unlikely to occur with the use of Org NC 45. It will hydrolyse mainly to its 3-hydroxy analogue which, like Org NC 45, possesses a wide margin between neuromuscular and vagal blocking doses. Org NC 45 has a high selectivity for the neuromuscular junction and represents a potentially useful addition to the armamen-tarium of clinically useful muscle relaxants. The synthesis and pharmacology of monoquater-nary 2/?, 16/?-dipiperidino-3a, 17/?-diacetoxy-5a-androstanes was first described by Buckett, Hewett and Savage (1973). The most potent of the monoquatemary compounds, Org NC 45, was shown to have about one-half to two-thirds of the potency and duration of action of the correspon-ding bisquaternary compound, pancuroniu