Thromb Haemost 1977; 37(01): 036-046
DOI: 10.1055/s-0038-1649199
Original Article
Schattauer GmbH

The Effect of Intravenous Adenosine Diphosphate on the Number of Circulating Platelets in Experimental Animals: Inhibition by Prostaglandin E1, Dipyridamole, SH-869 and VK-774

Ian B. Holmes
1  Biological and Medical Research Division, Sandoz Ltd., Basle, Switzerland
,
Gordon M. Smith*
1  Biological and Medical Research Division, Sandoz Ltd., Basle, Switzerland
,
Franz Freuler
1  Biological and Medical Research Division, Sandoz Ltd., Basle, Switzerland
› Author Affiliations
Further Information

Publication History

Received 30 June 1976

Accepted 25 October 1976

Publication Date:
03 July 2018 (online)

Summary

The number of circulating platelets was monitored in anaesthetized animals by a continuous flow technique, using a Technicon Autocounter®. Intravenous infusions of adenosine diphosphate (ADP) produced transient, dose-dependent falls in circulating platelet numbers in rabbits, dogs, rats, pigs and squirrel monkeys. The rat was the most sensitive of the species investigated.

In the rabbit, the effect of a submaximal dose of ADP was inhibited in a dose-dependent manner by intravenous infusions of prostaglandin E1 (PGE1), dipyridamole, and two derivatives of dipyridamole (SH-869 and VK-774). The dose-response curves for PGEl, SH-869 and VK-774 were approximately parallel, whereas that for dipyridamole was considerably less steep. PGE1 was the most potent inhibitor, but the duration of action was very short. Dipyridamole and SH-869 produced inhibition of long duration. The duration of action of VK-774 was intermediate.

All inhibitors produced marked and often long-lasting hypotension. The fact that no inhibition of ADP effects could be demonstrated with dibenzyline and hexamethonium, which also produced marked hypotension of long duration, indicated that inhibition of the ADP effect by the four antagonists studied was not due to changes in blood pressure.

* Present address: School of Pharmacy Robert Gordon’s Institute of Technology, Aberdeen, Scotland