Phenothiazine compounds enhance phentolamine effects on platelet aggregation and thromboxane B2 production.
In the present study we investigated the influence of phentolamine and the phenothiazine compounds chlorpromazine and trifluoperazine on human platelet aggregation as well as the effect of the association of phentolamine and the phenothiazines on responses to adenosine diphosphate, collagen, thrombin, ionophore A23187 and phorbol-myristate acetate, release reaction, thromboxane B2 synthesis and intraplatelet cyclic adenosine monophosphate levels. Phentolamine and phenothiazines exerted a dose-dependent inhibitory effect on aggregation induced by different concentrations of adenosine diphosphate and decreased the response to other agonists; furthermore, the phenothiazines enhanced the inhibitory effects of phentolamine on aggregation and thromboxane B2 synthesis, without influencing intraplatelet cyclic adenosine monophosphate levels. Phorbol ester-induced platelet activation was also inhibited in a dose-dependent way by each compound and by an association of phentolamine and phenothiazines, suggesting that the antiplatelet properties of these compounds might also be ascribed to intracellular events.
Anfossi
G
G
Department of Clinical and Biological Sciences, University of Turin, S. Luigi Gonzaga Hospital, Italy.
Trovati
M
M
Mularoni
E
E
Massucco
P
P
Cavalot
F
F
Mattiello
L
L
Emanuelli
G
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010646:Phentolamine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis* / Q000097:blood; D014268:Trifluoperazine / Q000494:pharmacology; D001620:beta-Thromboglobulin / Q000378:metabolism
D014150:Antipsychotic Agents; D010975:Platelet Aggregation Inhibitors; D001620:beta-Thromboglobulin; D014268:Trifluoperazine; D000001:Calcimycin; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D000242:Cyclic AMP; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002746:Chlorpromazine; D010646:Phentolamine