MR-14134, a new benzothiazepine with central hypotensive action

Pharmacology
P PrietoL S Román

Abstract

Structural changes introduced into the benzothiazepine molecule have led to a compound, MR-14134 (3-[(3-dimethylamino)propyl]-2,3,4,5- tetrahydro-2[4-methoxyphenyl]-1,5-benzothiazepin-4-one oxalate). We have compared the effects of MR-14134 and diltiazem on blood pressure and heart rate in anaesthetized and pithed rats following intravenous administration as well as in anaesthetized rats after intracerebroventricular administration and on the binding of [3H]clonidine in the rat cerebral cortex. MR-14134 (0.1-5.0 mg/kg, i.v.) produced a dose-dependent hypotensive and bradycardic effect similar in intensity but lasting longer than that of diltiazem. These effects were antagonized by previous administration of yohimbine but not by atropine, propranolol or ICI 118,551. Doses of 1 mg/kg i.v. of MR-14134 did not modify either blood pressure or heart rate in pithed rats and did not affect the hypertensive response elicited by electrical sympathetic stimulation or by exogenous administration of norepinephrine in pithed rats. Intracerebroventricular administration of MR-14134 (60 micrograms/kg) decreased blood pressure and heart rate in rats. This effect was antagonized by yohimbine and prazosin. [3H]Clonidine-binding experiments in the...Continue Reading

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