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INVESTIGATIONS TO CHARACTERIZE A NEW ANTI‐ARRHYTHMIC DRUG, ORG 6001, INCLUDING A SIMPLE TEST FOR CALCIUM ANTAGONISM
Author(s) -
SALAKO L.A.,
WILLIAMS E.M. VAUGHAN,
WITTIG J.H.
Publication year - 1976
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1976.tb07475.x
Subject(s) - procaine , chemistry , pharmacology , purkinje fibers , electrophysiology , medicine
1 The compound Org 6001 (3α‐amino‐2β‐hydroxy‐5α‐androstan‐17‐one hydrochloride) was found in recent experiments to exhibit anti‐arrhythmic activity. Evidence is presented in this paper concerning its mode of action. 2 Org 6001 was 1.8 times more potent than procaine as a local anaesthetic on desheathed frog nerve. 3 Org 6001 had no effect on the resting potential of isolated cardiac muscle of rabbit, but greatly reduced the maximum rate of depolarization (MRD). The action potential duration (APD) was marginally prolonged in atrial and ventricular muscle. 4 Org 6001 preferentially shortened APD in that part of the Purkinje system in which APD is normally longer than elsewhere, so that APD became more uniform throughout the ventricular conducting system. 5 Org 6001 did not block chronotropic responses to isoprenaline in atrial muscle. 6 Org 6001 had only a small negative inotropic effect in atrial muscle, and did not reduce the positive inotropic effect of raised calcium concentrations. 7 The effect of Org 6001 on MRD was reduced by lowering the external K + concentration. 8 It is concluded that Org 6001 is an anti‐arrhythmic drug of the first class (local anaesthetic type), and within this group is of a sub‐class more closely related to lignocaine than to quinidine.