Inhibition of long-chain fatty acid metabolism does not affect platelet aggregation responses
| Autor: | Scott R. Willoughby, Jennifer A. Kennedy, Geraldine A. Murphy, Yuliy Y. Chirkov, Larissa Chirkova, John D. Horowitz |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Blood Platelets Male Platelet Aggregation Vasodilator Agents Perhexiline Trimetazidine Amiodarone Pharmacology chemistry.chemical_compound Carnitine palmitoyltransferase 1 medicine Humans Carnitine O-palmitoyltransferase Carnitine Enzyme Inhibitors Aged Carnitine O-Palmitoyltransferase biology Chemistry Fatty Acids Cardiovascular Agents Middle Aged Biochemistry Enzyme inhibitor Case-Control Studies biology.protein Epoxy Compounds Female Etomoxir medicine.drug |
| Zdroj: | European Journal of Pharmacology. 356:207-213 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(98)00527-5 |
| Popis: | A number of anti-anginal agents (perhexiline, amiodarone, trimetazidine) have been shown to inhibit myocardial carnitine palmitoyltransferase-1, which controls access of long-chain fatty acids to mitochondrial sites of β-oxidation. In view of clinical data suggesting that perhexiline improves symptomatic status in unstable angina pectoris, and the known role of mitochondrial β-oxidation in platelet metabolism, we compared the platelet carnitine palmitoyltransferase-1 inhibitory and putative anti-aggregatory effects of perhexiline, amiodarone and trimetazidine with those of specific carnitine palmitoyltransferase-1 inhibitors: etomoxir and hydroxyphenylglyoxylate in both normal subjects and patients with stable angina. All of the compounds examined inhibited platelet carnitine palmitoyltransferase-1 activity; rank order of potency etomoxir>malonyl-CoA>hydroxyphenylglyoxylate>amiodarone≥ perhexiline>trimetazidine. However, only perhexiline, amiodarone and trimetazidine inhibited platelet aggregation. We conclude that (a) the carnitine palmitoyltransferase-1 inhibitors perhexiline, amiodarone and trimetazidine exert significant anti-aggregatory effects which may be therapeutically relevant and, (b) these effects are independent of carnitine palmitoyltransferase-1 inhibition. |
| Databáze: | OpenAIRE |
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