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Journal of Pharmacology And Experimental Therapeutics, Vol. 103, Issue 1, 10-23, 1951
Copyright © 1951 by American Society for Pharmacology and Experimental Therapeutics

THE ADRENERGIC BLOCKING ACTION OF SOME DIBENZAZEPINE DERIVATIVES

Lowell O. Randall 1 and Thomas H. Smith 1

1 Pharmacology Department, Hoffmann La Roche Inc., Nutley 10, New Jersey

Adrenergic blocking action has been measured in a series of eighteen dibenzazepine derivatives. Maximal action was found in the allyl dibenzazepine derivative, Ro 2-3248. Compounds with side-chains longer than propyl were inactive. The quaternary salts were inactive.

The allyl dibenzazepine derivative, Ro 2-3248, is a strong, short-acting adrenergic blocking agent which causes a prolonged fall of blood pressure. It is orally active. Ro 2-3248 blocked the stimulatory action of epinephrine on blood pressure, nictitating membrane and isolated seminal vesicles. It blocked the stimulatory effects of arterenol. It also blocked the effects of sympathetic nerve stimulation on the nictitating membrane and the carotid sinus reflex. It did not block the inhibitory actions of epinephrine on blood pressure, isolated tracheal rings and isolated intestine or the inhibitory action of isopropylarterenol on blood pressure. The compound has a relatively low toxicity.

Submitted on May 22, 1951




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Copyright © 1951 by the American Society for Pharmacology and Experimental Therapeutics.