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Journal of Pharmacology And Experimental Therapeutics, Vol. 94, Issue 2, 197-208, 1948
Copyright © 1948 by American Society for Pharmacology and Experimental Therapeutics

PHARMACOLOGY OF A NEW ANTIHISTAMINE, beta-PYRROLIDINE-ETHYL-PHENOTHIAZINE (PYRROLAZOTE)

MILTON J. VANDER BROOK 1, KENNETH J. OLSON 1, MARILYN T. RICHMOND 1, and MARVIN H. KUIZENGA 1

1 Research Division, The Upjohn Co., Kalamazoo, Michigan

1. Beta-pyrrolidineëthyl-phenothiazine monohydrochioride (Pyrrolazote) was compared with Pyribenzamine and demonstrated to be a potent antagonist to many of the pharmacologic responses of histamine. It was found to be effective for a longer period than Pyribenzamine as indicated by tests against histaminic spasms in vitro and protection against an aerosol of histamine in vivo.

2. Pyrrolazote was shown to possess antianaphylactic properties similar to those of Pyribenzamine.

3. Pyrrolazote neither enhanced nor antagonized the pressor effects of epinephrine in contradistinction to the enhancement produced by Pyribenzamine.

4. Acute toxicity studies in three species showed Pyrrolazote to be from one-half to one-twentieth as toxic as Pyribenzamine depending upon the route of administration and species used.

5. Chronic toxicity studies in rats showed that a dose of 10 mgm. per kgm. orally five days each week for ten weeks was innocuous. Histopathology limited to degenerative fatty infiltration of the liver occurred at doses of 25 mgm. per kgm. and greater.

Submitted on July 19, 1948




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Copyright © 1948 by the American Society for Pharmacology and Experimental Therapeutics.