Neuromuscular and other blocking actions of a new series of mono and bisquaternary aza steroids.

Abstract

Abstract The effects of a newly-synthesized series of mono and bisquaternary aza steroids have been investigated in the anaesthetized cat. All the compounds have been tested for neuromuscular blocking, ganglion blocking and vagolytic activity. The monoquaternary compounds of the series were weak neuromuscular blocking agents, their main action being to produce ganglion blockade and a fall in blood pressure. Both the bisquaternary compounds of the series primarily exhibited neuromuscular blocking activity of short duration and rapid onset. 4-Methyl-17 β-dimethylamino-4-aza-5α-androstane dimethiodide (HS-467) was approximately equipotent with tubocurarine as a neuromuscular blocking agent, whereas 17a-methyl-3β-pyrrolidino-17a-aza-D-homo-5-androstene dimethiodide (HS-310, chandonium iodide) was 4–5 times more active. Both compounds exhibited extremely weak ganglion blocking activity. Structure-activity relations are discussed, and it is concluded that in this series two quaternary heads are necessary for optimal neuromuscular blocking activity. The possibility that in the bisquaternary compounds interonium distance, or stereochemical conformation may be the main factor in determining specific neuromuscular blocking activity is discussed.