Steroidal monoquaternary ammonium salts with non-depolarizing neuromuscular blocking activity

Abstract

A series of ten 2β- or 3α-steroidal monoquaternary ammonium salts, having androstane or pregnane skeletons and related in structure to acetylcholine by possession of an oxygen function on the carbon atom next but one to the quaternary nitrogen atom, were investigated for neuromuscular blocking activity in vivo in the cat, hen and mouse and in vitro on the frog rectus muscle and on the rat phrenic nerve diaphragm preparation. All compounds displayed typical non-depolarizing activity, the duration of block being significantly less than that for (+)-tubocurarine in the cat and the hen. The potency of the salts was low with the most active compound, 3α-acetoxy-2β-piperidino-5α-androstan-17-one methobromide, being 1/16th as active on a molar basis in the cat as (+)-tubocurarine.