Some effects of disopyramide and its N-dealkylated metabolite on isolated nerve and cardiac muscle.

In animals and man the antidysrhythmic agent disopyramide in primarily metabolised by mono-N-dealkylation. The effects of disopyramide and its N-dealkylated metabolite (MIP) have been investigated using isolated cardiac and nervous tissue, and their effects have been compared with the effects of other antidysrhythmic agents. Disopyramide, d,l-propranolol and quinidine all decreased both maximum driving frequency and developed tension in electrically driven guinea pit atria. MIP and procaine amide also decreased maximum driving frequency, but had a positive intropic effect. MIP was only 4 times less active than disopyramide in decreasing maximum driving frequency. There was no evidence that either disopyramide or MIP possessed beta-adrenoceptor antagonist properties. In superfused rat sciatic nerves, it has been shown that neither disopyramide nor MIP possesses significant local anaesthetic properties. Procaine amide and lignocaine were highly active in this test. The possible contribution of MIP to the actions of disopyramide in vivo is discussed.