Presynaptic inhibitory effects of rocuronium and SZ1677 on [3H]acetylcholine release from the mouse hemidiaphragm preparation

It has been shown that nondepolarizing muscle relaxants may have effects on nicotinic acetylcholine receptors (nAChRs) other than those located on the skeletal muscle: some of them possess inhibitory effects on neuronal nAChRs [Anesth. Analg. 59 (1980) 935; Trends Pharmacol. Sci. 9 (1988) 16; Pharmacol. Ther. 73 (1997) 75]. It was shown that, e.g. (+)-tubocurarine and pancuronium are able to inhibit ACh release from the axon terminals of hemidiaphragm preparations and produce tetanic fade indicating their presynaptic effect. In this study rocuronium, a nondepolarizing steroidal muscle relaxant with shorter onset of action, and SZ1677 [1-(3-hydroxy-17β-acetyloxy)-2β-(1.4-dioxa-8-azaspiro-[4,5]-dec-8-yl)-(5-androstane-16β-yl)-1-(2-propenyl) pyrrolidinium bromide], a short-acting muscle relaxant [Ann. New York Acad. Sci. 757 (1995b) 84] inhibited the release of ACh in response to axonal stimulation, while -bungarotoxin failed to reduce the stimulation evoked release of ACh and did not produce tetanic fade. These results indicate that in addition to their postsynaptic effect, rocuronium and SZ1677 have presynaptic inhibitory effects on neuronal nAChRs at the neuromuscular junction. The finding that -bungarotoxin does not inhibit the release and does not produce tetanic fade indicates that it possesses affinity only for the postsynaptic muscle nAChRs.