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https://hdl.handle.net/2440/8816
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Type: | Journal article |
Title: | Inhibition of long-chain fatty acid metabolism does not affect platelet aggregation responses |
Author: | Willoughby, S. Chirkov, Y. Kennedy, J. Murphy, G. Chirkova, L. Horowitz, J. |
Citation: | European Journal of Pharmacology, 1998; 356(2-3):207-213 |
Publisher: | Elsevier |
Issue Date: | 1998 |
ISSN: | 0014-2999 1879-0712 |
Statement of Responsibility: | Scott R. Willoughby, Yuliy Y. Chirkov, Jennifer A. Kennedy, Geraldine A. Murphy, Larissa P. Chirkova, John D. Horowitz |
Abstract: | 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 beta-oxidation. In view of clinical data suggesting that perhexiline improves symptomatic status in unstable angina pectoris, and the known role of mitochondrial beta-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 > or = 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. |
Keywords: | Perhexiline Amiodarone Trimetazidine Platelet aggregation Carnitine palmitoyltransferase-1 Etomoxir |
Rights: | Copyright © 1998 Elsevier Science B.V. All rights reserved. |
DOI: | 10.1016/S0014-2999(98)00527-5 |
Published version: | http://dx.doi.org/10.1016/s0014-2999(98)00527-5 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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