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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: Behavioural Processes, 1998; 356(2-3):207-213
Publisher: Elsevier
Issue Date: 1998
ISSN: 0014-2999
Statement of
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
Platelet aggregation
Carnitine palmitoyltransferase-1
Rights: Copyright © 1998 Elsevier Science B.V. All rights reserved.
DOI: 10.1016/S0014-2999(98)00527-5
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