Antihistaminic drug bromadryl and stimulated platelet aggregation.
The H1-receptor antagonist bromadryl dose-dependently inhibited stimulated rat platelet aggregation in vitro. Bromadryl was 10 times more effective on the secondary aggregation of thrombin-stimulated platelets compared with its inhibition of ADP-stimulated primary platelet aggregation in plasma. The inhibition of aggregation was accompanied by a dose-dependent inhibition of thrombin-stimulated malondialdehyde formation and thromboxane B2 production. The results indicate that bromadryl may interfere intracellularly with membrane phospholipid peroxidation and the arachidonic acid metabolism of stimulated platelets. Bromadryl, like other cationic amphiphilic drugs, may inhibit stimulated platelet functions by decreasing the stimulus-induced activation of phospholipase A2. Our results support the possible interference of bromadryl with histamine as an intraplatelet messenger responsible for aggregation.
Nosál
R
R
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Jancinová
V
V
Petríková
M
M
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004155:Diphenhydramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood
D006634:Histamine H1 Antagonists; D010975:Platelet Aggregation Inhibitors; D008315:Malondialdehyde; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D004155:Diphenhydramine; D013917:Thrombin; C005715:embramine