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Journal of Pharmacology And Experimental Therapeutics, Vol. 171, Issue 2, 276-287, 1970
Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics

GENERAL PHARMACOLOGIC ACTIONS OF THE ANTIHYPERTENSIVE AGENT 2,6-DICHLOROBENZYLIDENE AMINOGUANIDINE ACETATE (WY-8678)

THOMAS BAUM 1, ALLEN T. SHROPSHIRE 1, GARY ROWLES 1, RONALD VAN PELT 1, SUSAN P. FERNANDEZ 1, DONALD K. ECKFELD 1, and MELVYN I. GLUCKMAN 1

1 Pharmacological Evaluation Section, Wyeth Laboratories, Inc., Radnor, Pennsylvania

Wy-8678 has been shown to lower blood pressure and heart rate in unanesthetized hypertensive animals. The present study describes the general cardiovascular actions of the compound. Intravenous injection of Wy-8678 caused an initial increase in blood pressure followed by a prolonged fall and a decrease in cardiac output, contractile force and heart rate in anesthetized dogs. The negative inotropic and chronotropic actions required the presence of sympathetic tone. Wy-8678 inhibited pressor responses to various procedures which initiate general sympathetic discharge. The compound also antagonized responses to sympathetic nerve stimulation, particularly at low frequencies. It is concluded that the hypotensive effect may result from inhibition of sympathetic tone by an action at nerve endings or more central sites.

Submitted on June 12, 1969
Accepted on October 20, 1969




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Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics.