A comparison of the pharmacological activities of tertiary bases and their quaternary ammonium derivatives

A study has been made of some pharmacological actions of tertiary amine analogues of drugs known to be active in the quaternary salt form. Tertiary amine analogues of acetylcholine, carbachol,m-bromophenyl-2-dimethylaminoethyl ether methobromide, neostigmine, hexamethonium and 4-dimethylamino-methyl-2-methyl-1,3-dioxolane methiodide were prepared and tested pharmacologically.

It was found that the presence of a quaternary ammonium group was essential for high muscarinic activity in acetylcholine, carbachol and the dioxolane and also for cholinesterase inhibiting activity in neostigmine. Tertiary amine analogues of acetylcholine retained some nicotinic activity at the neuromuscular junction and also some cholinesterase substrate activity. Nicotinic activity at the neuromuscular junction or at autonomie ganglia was not retained by the pyrrolidine analogue ofm-bromophenyl-2-dimethylamino ether methobromide. The pyrrolidine analogue of carbachol was similarly inactive at the neuromuscular junction but showed weak ganglion-stimulating activity. In the hexamethonium series quaternary salts and tertiary bases did not differ greatly in ganglion-blocking potency.

The active tertiary amines were tested for behavioural effects in the open-field test but no evidence for appreciable central activity was found.