METHYLSEROTONINS AS POTENT ANTIMETABOLITES OF SEROTONIN ACTIVE BOTH IN VITRO AND IN VIVO

¹ The Rockefeller Institute for Medical Research, New York, New York

2,5-Dimethylserotonin was a water-soluble and rather active antiserotonin which was effective not only on isolated artery rings and isolated uteri, but also as an antagonist to the pressor action of serotonin in dogs. In these animals most individuals were protected against the pressor effects of 0.5-1.0 mgm. of serotonin by approximately 1 mgm. of the analog per kgm. The compound was effective either intravenously or orally, but was considerably less efficient by the oral route. Other pharmacological properties of it were recorded. A series of other methylserotonins, including 1,5-dimethylserotonin, 2,5-dimethylbufotenine, 1,2,5-trimethylserotonin and 1-benzyl-2,5-dimethylserotonin were studied both in isolated rat uterus and in living dogs. By the intravenous route in dogs, these (except the 1-benzyl compound) were less active than 2,5-dimethylserotonin as an antagonist to the pressor effect, but some had other interesting properties. Thus, 1,5-dimethylserotonin showed a considerable amount of serotonin-like activity on the rat uterus, and the benzyl compound exerted an irreversible antagonism in this tissue. 1-Benzyl-2,5-dimethylserotonin was extraordinarily active when fed to dogs and at 1 mgm. per kgm. per day by the oral route it protected them. It was therefore the most powerful known antiserotonin which was orally effective against the pressor action of the hormone.

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