'In vitro' and 'ex vivo' effects of picotamide, a combined thromboxane A2-synthase inhibitor and -receptor antagonist, on human platelets
| Autor: | M. De Cunto, S. Grasselli, G.G. Nenci, M. Berrettini, P. Parise |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Adult
Blood Platelets Male Platelet Aggregation medicine.drug_class Receptors Prostaglandin Receptors Thromboxane Phthalic Acids Arachidonic Acids Pharmacology chemistry.chemical_compound Thromboxane A2 Malondialdehyde Cyclic AMP medicine Humans Picotamide Pharmacology (medical) Platelet Arachidonic Acid Dose-Response Relationship Drug Prostanoid General Medicine Receptor antagonist In vitro Prostaglandin Endoperoxides Synthetic Thromboxane B2 chemistry 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid Female Arachidonic acid Thromboxane-A Synthase Platelet Aggregation Inhibitors Ex vivo medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 39:495-500 |
| ISSN: | 1432-1041 0031-6970 |
| Popis: | Picotamide (G 137), a new non prostanoid inhibitor of in vitro arachidonic acid induced platelet aggregation, has been further characterized in in vitro and ex vivo studies. When whole blood was activated with collagen in the presence of picotamide 5 x 10(-4) M, thromboxane B2 production was decreased, and 6-keto-PGF1 alpha generation was significantly increased, suggesting a reorientation of platelet endoperoxide metabolism following blockade of thromboxane synthetase. Picotamide also inhibited platelet aggregation and clot retraction induced by the endoperoxide analogue U46619 in human platelets, indicating thromboxane A2-receptor antagonism, possibly of competitive nature. A single oral dose of picotamide 1 g in 24 healthy volunteers produced a significant inhibition of collagen, arachidonic acid and U46619-induced platelet aggregation. Serum levels of thromboxane B2 were also reduced. Chronic administration of picotamide 1.2 g/d to patients with vascular disease resulted in a prompt and persistent fall in their increased plasma levels of beta-thromboglobulin. The results indicate that picotamide is a combined thromboxane B2-synthetase inhibitor and thromboxane A2-receptor antagonist in human platelets, and that it may prove useful as an antithrombotic agent. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink