Anticholinesterase and antiacetylcholine activity of 1-phenylcyclohexylamine derivatives

The antiacetylcholine and anticholinesterase potencies of four 1-phenylcyclohexylamine derivatives were estimated by measuring their antagonism to the contractile response of smooth and striated muscles, and their inhibition of cholinesterase activity. In addition, their affinities towards the central muscarinic receptor from mouse brain homogenate were determined by competition experiments in vitro. Relative to atropine, these drugs exerted mild antimuscarinic activity in both isolated smooth muscle and in the competition experiments. On the other hand, they were found to exert antinicotinic potencies equal to that of d-tubocurarine in the striated muscle. The concentration of (³H)-phencyclidine taken up by mouse brain in vivo could be correlated with its dissociation constants from the central muscarinic binding sites, as well as with the Ki values for acetylcholinesterase inhibition, both determined in vitro. Since these drugs have a similar rigid spatial molecular structure, it is proposed that the variations in the potency of their cholinergic interactions stemmed mainly from the structural changes in the region of the 'cationic head'.