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Journal of Pharmacology And Experimental Therapeutics, Vol. 129, Issue 1, 1-10, 1960
Copyright © 1960 by American Society for Pharmacology and Experimental Therapeutics

THE ACTIONS OF DICHLOROISOPROTERENOL IN THE DOG HEART-LUNG PREPARATION AND THE ISOLATED GUINEA-PIG ATRIUM

W. W. Fleming 1 and D. F. Hawkins 2

1 Department of Pharmacology, West Virginia University Medical School, Morgantown, West Virginia
2 Hammersmith Hospital, Du Cane Road, London W12, England

Dichloroisoproterenol in doses of 0.01 to 3 mg has the properties of a sympathomimetic amine in the dog heart-lung preparation, causing positive chronotropic, inotropic and dromotropic effects and increasing coronary flow. Subsequently, larger doses are depressant, producing negative chronotropic and inotropic effects. Positive chronotropic and inotropic effects with small doses and negative chronotropic and inotropic effects with large doses were also observed in the isolated guinea-pig right atrium. The response to a single dose is long lasting in both preparations, not transient as is the case with epinephrine or norepinephrine. In these respects the actions of DCI are very similar to those of ephedrine.

The postulated mechanism of the interaction of DCI with either epinephrine or norepinephrine in the heart is more properly termed competitive dualism than adrenergic blockade, since doses of DCI smaller than those which demonstrate sympathomimetic actions do not interact with epinephrine or norepinephrine.

In the presence of large amounts of DCI, epinephrine and norepinephrine produce a fall in heart rate in both preparations. This effect is blocked by atropine but not by hexamethonium. It is not potentiated by physostigmine.

Submitted on October 30, 1959




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