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Canadian Journal of Anesthesia, Vol 23, 36-47, Copyright © 1976 by Canadian Anesthesiologists' Society

Studies on Fazadinium Bromide (AH 8165): A New Non-Depolarizing Neuromuscular Blocking Agent

R. HUGHES 1, J. P. PAYNE 2, and N. SUGAI 3

1 Research Department of Anaesthetics, Royal College of Surgeons of England, Lincoln's Inn Fields, London WC2A 3PN
2 St. Peter's Hospital, London WC2
3 Department of Pharmacology, The Wellcome Research Laboratories, Beckenham, Kent

Intravenous dose-response relationships were used to correlate neuromuscular paralysis with the effects of fazadinium (AH 8165) on autonomic mechanisms in anaesthetized cats and rhesus monkeys and with cardiovascular effects in man. In cats and monkeys neuromuscular paralysis of the twitch responses of the gastrocnemius muscle by fazadinium was accompanied by impairment of the vagally induced bradycardia, but cardiovascular disturbances were small. Blockade of sympathetic mechanisms and hypotension were only evident with supra-maximal doses. In man tachycardia was a common occurrence and in some patients hypertension occurred with doses of the drug needed for complete neuromuscular paralysis.

Fazadinium was three to four times more potent in rhesus monkeys than in cats and its course of action was considerably longer. The potency of the drug in man corresponded more closely to that in cats than in rhesus monkeys but its course of action in patients was similar to that in monkeys.

In man, dose-response curves were constructed for the contractions of the adductor pollicis muscles elicited by tetanic and single twitch stimuli applied to the corresponding ulnar nerves. The onset of paralysis of the tetanic contractions after the intravenous injection of fazadinium (0.4 mg/kg) occurred within two minutes, but recovery was slow and about 50 minutes were needed for its completion. Depression of the simultaneously recorded twitch responses was less marked, slower in onset and recovery was slightly more rapid. These effects were similar to those obtained with tubocurarine (0.2 mg/kg) but the action of fazadinium was slightly shorter.

Tetanic-tension ratios were computed after 30 and 50 per cent recovery from neuromuscular blockade in man. These ratios were lower with fazadinium than with tubocurarine and indicated that tetanic fade was greater and more persistent after fazadinium than after tubocurarine.






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Copyright © 1976 by the Canadian Anesthesiologists' Society.