Phenothiazines inhibit collagen-induced thromboxane B2 synthesis and increase forskolin anti-aggregating effects in human platelets.
1. The aim of the present study was to investigate the effects of phenothiazine compounds chlorpromazine and trifluoperazine on human platelet response to collagen and sodium arachidonate. 2. The results demonstrated that phenothiazines inhibit collagen-induced platelet aggregation and thromboxane B2 synthesis in a dose-dependent way and increase the antiaggregating properties of forskolin. 3. Phenothiazines at high concentrations decreased the platelet aggregation in response to arachidonate, without a significant reduction of thromboxane B2 production. 4. The data provides evidence that phenothiazine effects could involve calmodulin-dependent enzymatic activities.
Department of Clinical and Biological Sciences, University of Turin, Italy.
G
G
Anfossi
P
P
Massucco
E
E
Mularoni
F
F
Cavalot
S
S
Burzacca
L
L
Mattiello
M
M
Trovati
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis*; D014268:Trifluoperazine / Q000494:pharmacology
D014150:Antipsychotic Agents; D010975:Platelet Aggregation Inhibitors; D005576:Colforsin; D014268:Trifluoperazine; D016718:Arachidonic Acid; D013929:Thromboxane B2; D003094:Collagen; D000242:Cyclic AMP; D002746:Chlorpromazine