EFFECTS OF SKF-385 AND RESERPINE ON THE TISSUE CATECHOLAMINE CONTENT IN RABBITS

Abstract

The intravenous injection of 0.5 to 3.0 mg/kg of traps-2-phenylcyclopropylamine maleate (SKF-385) in the anesthetized dog produces the pressor effect which is prevented by the adrenolytic doses of tolazoline and dibenamine (1). However, the repetition of the doses of SKF-385 exerts the depressor effect which is totally abolished by the pretreatment with reserpine. The results indicate that the pressor effect relates with the release of the endogenous noradrenaline, while the depressor effect relates with the presence of the endogenous noradrenaline in the circulatory organs. The accumulation of the endogenous catecholamine after administration of monoamine oxidase (MAO) inhibitor has been shown in the central nervous system (2-4) and in the heart (5-7). On the other hand, the administration of iproniazid has been reported to produce no significant change of the brain noradrenaline in rabbit (8, 9) and of the heart noradrenaline in rabbit and mouse (9, 10). Goldberg and Shideman (11) have shown that the myocardial noradrenaline in cat decreases significantly in response to 2 to 30 mg/kg of SKF385, while that in rat increases markedly.
Tachi, Nakatani and Fujiwara (12) have studied the effects of reserpine on the isolated atrial preparation of rabbit pretreated with the MAO inhibitors. The atrium of rabbit pretreated with beta-phenylisopropylamine or SKF-385, either of which alone produces the positive inotropic and 'chronotropic effects, has responded to reserpine with the depressor effect, while the atrium of rabbit pretreated with iproniazid has responded to reserpine with the augmenting effect. The results prompted to study the changes of catecholamine in the tissues including brain, heart, spleen and adrenal glands in the rabbit which received SKF-385 alone or reserpine after the pretreatment with SKF-385.