Antiacetylcholine Action of Imipramine

Abstract

Imipramine, a potent antidepressive drug has been shown to antagonize the actions of a number of autopharmacological substances like histamine, 5-hydroxytryptamine, bradykinin, catecholamines and acetylcholine (1). Sigg and his coworkers (2, 3) observed a dual effect of imipramine on the various manifestations of the autonomic nervous system; a blocking action at higher dosage and a stimulant effect with low concentrations. The purpose of the present study was to investigate in more details the interactions between imipramine and acetylcholine at various sites, where acetylcholine is the neurotransmitter. This was done both at the muscarinic and nicotinic site. MATERIALS AND METHODS Studies on muscarinic sitesSmooth muscle preparations of several species of laboratory animals were studied. Tissues were mounted in an isolated organ bath in oxygenated Ringer Locke solution at 37± 1'C unless otherwise mentioned. i) Intestinal smooth muscle: Ileum of rabbit and guinea-pig, rat colon and taenia coli of guinea-pig were used. Imipramine was added to the bath in a concentration of 1 x 10-6 to 1 x 10-5 g/ml.ii) Guinea pig vas deferens and rat uterus : The latter being suspended i n de Jalon solu tion at 22"C. Imipramine was used in the same range as before .iii) Cardiac muscle : Isolated rabbit and frog hearts were employed for this purpose . The rabbit heart was perfused with Ringer Locke solution at 37±0 .5°C, using Langen dorff's preparation. The frog heart was perfused with frog Ringer solution . Imipramine (10-6 g/ml) was added to the perfusing fluid.iv) Blood pressure : Mongrel dogs (6-14 kg), cats (2.5-4 kg) and albino rats (200 275 g) of either sex were employed for this purpose. Animals were anaesthetized with pentobarbitone sodium (30 mg/kg i.p.). Carotid blood pressure was recorded by a mer cury manometer on a smoked kymograph paper and drugs were injected through the can nulated femoral vein in the case of dogs and cats, and jugular vein in rats. Imipramine was administered in a dose range of 0.5 to 5 mg/kg in all experiments .Studies on nicotinic sites A) Neuro-muscular junction i) Sciatic-gastrocnemius preparation in the cat: Cats (3-4.5 kg) of either sex were anaesthetized with pentobarbitone sodium (30 mg/kg), and were maintained on positive