Antagonists discriminate muscarinic excitation and inhibition in sympathetic ganglion.

The effect of muscarinic antagonists was studied on the muscarinic slow IPSP (inhibitory postsynaptic potential) and slow EPSP (excitatory postsynaptic potential) in bullfrog sympathetic ganglia using the sucrose-gap recording method. Pirenzepine, alcuronium and atropine reduced slow IPSP amplitude more than slow EPSP amplitude. The most selective antagonists studied were pancuronium and gallamine which blocked or substantially reduced the slow IPSP without significantly affecting slow EPSP amplitude. The results suggest that the muscarinic inhibitory response may involve a different muscarinic receptor subtype, and/or receptor-ion-channel complex, than the muscarinic excitatory response.

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 C16 monoquaternary 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 anticholinesterases 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 armamentarium of clinically useful muscle relaxants.