Effects of an aminosteroid, ORG 6001, on various membrane phenomena of non-myelinated nerve fibres of the rat.

The aminosteroid ORG 6001 (3 alpha-amino-5 alpha-androstan-2 beta-ol-17-one hydrochloride) was shown to be a compound with a rather strong local anaesthetic action. Compound action potentials evoked in non-myelinated nerve fibres of the desheathed rat vagus with the single sucrose gap method showed, in presence of this drug, a decrease in amplitude and increase in conduction time comparable with the effect of lidocaine. Since the total membrane resistance represented by the amplitude of the electrotonic potential was not affected by ORG 6001, it is likely that ORG 6001 reduces the transient increase in sodium conductance during the action potential, a mechanism also postulated for lidocaine. This is confirmed by the decrease of the post-tetanic hyperpolarization in the presence of both ORG 6001 and lidocaine. Since neither sodium pump activity nor the Na/K coupling ratio was affected by ORG 6001, the increase of the potassium-activated response was explained by an increased sodium permeability during rest. The local anaesthetic action of these drugs was even seen with a concentration (20--40 micron) sufficient to produce antiarrhythmic effects in vivo in man if the nerve was stimulated frequently (1--4 c.p.s.).