STERIC CONFIGURATION AND THE ACTIVITY AT THE MAMMALIAN NEUROMUSCULAR JUNCTION OF CYCLIC AMINOALCOHOL DERIVATIVES

¹ Naval Medical Research Institute, National Naval Medical Center, Bethesda, Maryland

Two series of cyclic aminoalcohols have been studied for the effects of steric configuration on activity at the mammalian neuromuscular junction. The compounds are: cyclopentyltrimethylammonium ion, cyclohexyltrimethylammonium ion and two stereoisomeric pairs, cis-and trans-2-hydroxycyclopentyltrimethylammonium ions and cis- and trans-2-hydroxycyclohexyltrimethylammonium ions. Their actions on the intact cat, the in vitro kitten phrenic nerve-diaphragm and the chronically denervated cat muscle are described.

Marked differences in potency were found. The nonhydroxylated amine was the most potent, and the trans hydroxy isomer the least potent in each series.

The mutual interaction of the compounds was investigated. The trans isomers were found to be able to antagonize the effects of the other members of the series, but the effects of cis isomers were additive with the other members.

The bases for these relationships are discussed in terms of the steric structures of the compounds. The conclusion is reached that the receptors may be sheltered by adjacent structures which function either by sterically hindering the approach to the receptor or by reacting with the hydroxyl group to the detriment of interaction with the onium group.