Neuromuscular blocking and antimuscarinic activity of a series of bis-atropinium and N-n-alkyl atropinium compounds.

Abstract

Abstract Measurements of neuromuscular blocking and antimuscarinic activity have been made in a series of bis-atropinium (BA) and N-n-alkyl atropinium (N-AA) compounds. That the second atropinium group contributed to the neuromuscular blocking activity of BA compounds was shown by the relative lack of such activity in the N-AA series of compounds. Peak neuromuscular blocking activity occurred when two atropinium groups were separated by a chain of either 10 or 11 methylene groups. Members of both series of compounds displayed antimuscarinic properties but estimates of activity differed according to whether they were obtained by determination of affinity constants on guinea-pig isolated ileum or production of mydriasis in mice. From measurements of affinity constant on the guinea-pig ileum it is concluded that BA compounds interact with only one muscarinic receptor. However, the high activity of the deca- and undecamethylene BA compounds in producing mydriasis suggest that these compounds possibly interact with two receptors at once.