Influence of propranolol and 4-hydroxypropranolol on platelet aggregation and thromboxane A2 generation.
We examined in vitro effects of propranolol and its major metabolite, 4-hydroxypropranolol, on human platelets. Both propranolol and its 4-hydroxy metabolite had no significant direct effect on either platelet aggregation or TXA2 generation in therapeutic concentrations. Higher concentrations (greater than or equal to 10 micrograms/ml), however, reduced both parameters of platelet function. When propranolol and 4-hydroxypropranolol were incubated in combination with platelets in equal concentrations, there were synergistic effects on platelet aggregation and TXA2 generation. Neither propranolol nor 4-hydroxypropranolol inhibited platelet aggregation or TXA2 synthesis in sonicated platelets at any concentration, indicating that intact platelet membrane is necessary for their action.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology; D002462:Cell Membrane; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D011433:Propranolol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D013931:Thromboxanes; C001422:4-hydroxypropranolol; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D011433:Propranolol; D004837:Epinephrine