Dm. Patelunashoffman et al., ANALYSIS OF THE POTASSIUM CHANNEL OPENERS CELIKALIM, PINACIDIL AND CROMAKALIM IN PLATELET MODELS OF THROMBOSIS, Thrombosis research, 74(5), 1994, pp. 441-452
The antihypertensive agents pinacidil, cromakalim and celikalim lower
blood pressure by opening potassium channels in vascular smooth muscle
. The role of these compounds in inhibiting human platelet aggregation
and preventing white thrombus formation in a rabbit arteriovenous shu
nt model was examined. None of these agents (100 mu M), substantially
inhibited platelet aggregation induced by epinephrine or arachidonic a
cid. Only celikalim (100 mu M) inhibited collagen (45%), ADP (56%), or
serotonin (61%) induced platelet aggregation and ADP- (41%) or epinep
hrine-potentiated (61%) serotonin-induced platelet aggregation. Celika
lim inhibited white thrombus formation at i.v. doses of 0.25 mg/kg (46
% inhibition) but not 0.1 mg/kg; (14.6%); equihypotensive doses of pin
acidil (0.5 mg/kg; 21.7%) and cromakalim (0.2 mg/kg, 7.5%; 0.4 mg/kg,
33%) were less effective. Glyburide (i.v. dose of 0.5 mg/kg) inhibited
the antithrombotic activity of celikalim and to a lesser extent croma
kalim. The greater antithrombotic activity of celikalim in vivo may be
related to beneficial effects on blood theology and reduced red blood
cell deformability.