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- W2502180238 endingPage "1059" @default.
- W2502180238 startingPage "1049" @default.
- W2502180238 abstract "Introduction: The re-purposing of the anti-anginal drug perhexiline (PHX) has resulted in symptomatic improvements in heart failure (HF) patients. The inhibition of carnitine palmitoyltransferase-1 (CPT-1) has been proposed as the primary mechanism underlying the therapeutic benefit of PHX. This hypothesis is contentious.Areas covered: We reviewed the primary literature and patent landscape of PHX from its initial development in the 1960s through to its emergence as a drug beneficial for HF. We focused on its physico-chemistry, molecular targets, tissue accumulation and clinical dosing.Expert opinion: Dogma that the beneficial effects of PHX are due primarily to potent myocardial CPT-1 inhibition is not supported by the literature and all available evidence point to it being extremely unlikely that the major effects of PHX occur via this mechanism. In vivo PHX is much more likely to be an inhibitor of surface membrane ion channels and also to have effects on other components of cellular metabolism and reactive oxygen species (ROS) generation across the cardiovascular system. However, the possibility that minor effects of PHX on CPT-1 underpin disproportionately large effects on myocardial function cannot be entirely excluded, especially given the massive accumulation of the drug in heart tissue." @default.
- W2502180238 created "2016-08-23" @default.
- W2502180238 creator A5007543851 @default.
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- W2502180238 creator A5017275427 @default.
- W2502180238 creator A5028787260 @default.
- W2502180238 creator A5059782849 @default.
- W2502180238 date "2016-07-25" @default.
- W2502180238 modified "2023-09-25" @default.
- W2502180238 title "Pleiotropic mechanisms of action of perhexiline in heart failure" @default.
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