Dependence of the antagonism at human platelet 5-HT2 receptors by ketanserin on the reaction pH.

Abstract:

:The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9) M; pH 8.6: 4.5 X 10(-6) M) being found for ketanserin. With such an alkaline pH-shift, the fraction of the ionized form of the drugs decreased, reduction of the inhibitory capacity and of the ionized fraction being strongly correlated. Ketanserin (40 mg orally, - 15 h) in human volunteers, completely inhibited the 5-HT-induced platelet aggregation measured ex vivo, when tested at a reaction pH of 7.4; without gassing with CO2 5% -O2 95%, the plasma pH became alkaline and the inhibitory potency of the drug was strongly reduced (-60%). This study demonstrates the importance of the reaction pH for the aggregation of human platelets induced by 5-HT and its inhibition by ketanserin.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

De Clerck F,Xhonneux B,Tollenaere JP,Janssen PA

doi

10.1016/0049-3848(85)90297-x

subject

Has Abstract

pub_date

1985-12-01 00:00:00

pages

581-96

issue

5

eissn

0049-3848

issn

1879-2472

pii

0049-3848(85)90297-X

journal_volume

40

pub_type

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