Inhibition of long-chain fatty acid metabolism does not affect platelet aggregation responses.
Eur J Pharmacol
; 356(2-3): 207-13, 1998 Sep 04.
Article
em En
| MEDLINE
| ID: mdl-9774251
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Fármacos Cardiovasculares
/
Carnitina O-Palmitoiltransferase
/
Agregação Plaquetária
Tipo de estudo:
Observational_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
1998
Tipo de documento:
Article