Nicotinic stimulant action of some tolyl and xylyl analogues of 1,1-dimethyl-4-phenylpiperazinium (DMPP).

ABSTRACT

1. The nicotinic stimulant properties of DMPP have been compared with those of its ortho-, meta- and para-tolyl analogues, and its 2,6- and 3,5-xylyl analogues, on the blood pressure of the cat and on the semispinalis cervicis muscle of the chick.2. A single ortho-methyl group does not significantly change the nicotinic activity, but two such groups greatly reduce or abolish activity. Meta- or para-methyl substitution reduces activity, but does not abolish it.3. The effect on nicotinic activity of methyl substitution in the phenyl ring of DMPP closely parallels the effect of ring-methyl substitution in phenyl choline ether.4. Ortho-methyl substitution has been shown spectroscopically to alter markedly the spatial orientation of the phenyl ring of DMPP relative to the piperazine ring. The effect of these conformational changes on nicotinic activity is discussed in relation to a recent hypothesis concerning the conformation of acetylcholine required for interaction with nicotinic receptors.5. The compounds tested had no muscarinic activity on the isolated guinea-pig ileum.