Pharmacology of Org NC 45 Compared with Other Nondepolarizing Neuromuscular Blocking Drugs

Abstract

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.

The effect of gallamine, gallopamil and nifedipine on responses to acetylcholine and carbachol in the taenia of the guinea‐pig caecum

“…(Hobbiger et al, 1969;Nasu & Urakawa, 1973) and ganglion blocking activity of gallamine is only observed in other smooth muscle preparations of the guinea-pig with higher concentrations than were used in taenia (Birmingham & Hussain, 1980). Another possible reason for the difference is that the anticholinesterase activity of gallamine (Marshall et al, 1980) could counteract the inhibition of responses to ACh, but pretreatment of the tissue with the irreversible anticholinesterase paraoxon did not increase the inhibitory effect of gallamine on responses to ACh.…”

Histological investigations of muscle atrophy and end plates in two critically ill patients with generalized weakness

“…These three drugs affect neuromuscular transmission. Vecuronium bromide, a pancuronium analogue (Bowman 1983;Marshall et al 1980), causes like ( + )-tubocurarine a powerful mainly postsynaptic blockade of neuromuscular transmission, by a non-depolarizing competitive antagonism with acetylcholine for the AChR (Standaert 1984). The neuromuscular blocking properties of the aminoglycosides and of clindamycin are less powerful (Argov and Mastaglia 1979;Torda 1980;Sokoll and Gergis 1981).…”

The influence of stimulation parameters on the potency and reversibility of neuromuscular blocking agents

“…Since the in vitro rate of dissociation of Org-NC45 is not different from that of pancuronium its shorter in vivo duration of action than that of pancuronium may be due to differences in tissue distribution (Van der Veen and Bencini, 1980), metabolism (Marshall, Agoston, Booij, Durant, and Foldes, 1980) and excretion of the compounds.…”