Selective pharmacological blockade of parasympathetic and enteric ganglia

Abstract

The blocking effects of two newly synthetized compounds, diisopropyldecylammonium iodide (IEM-1194) and 2,2,6,6-tetramethyldecylpiperidinium chloride (IEM-1559), on insulin- and pentagastrin-induced gastric secretion in chronic dogs, on stress-induced changes in gastric mucosa in rats, on vagus-induced effects in heart and intestine, on arterial blood pressure and on synaptic transmission through isolated ciliary and superior cervical ganglia in cats were studied. The effects observed were compared with those produced by hexamethonium (C 6), a conventional ganglionic blocking agent. Both IEM-1194 and IEM-1559 inhibited gastric secretion and acid output for a much longer time than C 6 did and effectively protected gastric mucosa against stress-induced erosions and hemorrhages. IEM-1194 blocked the vagus-induced decrease in heart rate and increase in duodenal motility for a longer time than did C 6 and also, in contrast to C 6, did not reduce the arterial blood pressure. The blockade of synaptic transmission through isolated ciliary and superior cervical ganglia produced by IEM-1194 and IEM-1559 was characterized by lower EC 50 and was more prolonged than that produced by C 6. In addition, both IEM-1194 and IEM-1559 were more potent blocking agents in ciliary ganglion than in superior cervical ganglion. It is suggested that IEM-1194 and IEM-1559 are selective blocking agents for parasympathetic and enteric ganglia versus sympathetic ganglia.