By the drug repositioning strategy, we confirmed that perhexiline maleate (Pex) potentially ameliorates heterotopic ossification in model cells and mice. (biomedcentral.com)
Antianginal agent perhexiline2
therefore, the Cis-hydroxyperhexiline/perhexiline concentration ratio may be useful for optimizing individual patient treatment with the antianginal agent perhexiline. (wikipedia.org)
The cytochrome P450 (P450)-mediated 4-monohydroxylations of the individual enantiomers of the racemic antianginal agent perhexiline (PHX) were investigated in human liver microsomes (HLMs) to identify stereoselective differences in metabolism and to determine the contribution of the polymorphic enzyme CYP2D6 and other P450s to the intrinsic clearance of each enantiomer. (aspetjournals.org)
Racemic2
Racemic perhexiline has been used (or is currently undergoing clinical trials) for the treatment of a variety of cardiovascular disorders. (elsevierpure.com)
Perhexiline (PHX) is administered as a racemic mixture and exhibits enantioselective pharmacokinetics in both poor and extensive metabolizers of CYP2D6 (PM and EM, respectively). (edu.au)
Enantiomers2
Here, we report the first asymmetric synthesis of both enantiomers of perhexiline in high enantiomeric excess and the assignment of their (-)-S/(+)-R absolute stereochemistry by X-ray crystallography. (elsevierpure.com)
To determine the steady-state pharmacokinetics of perhexiline (PHX) enantiomers over one interdosing interval in CYP2D6 extensive and poor metabolizer (EM and PM, respectively) patients administered rac-PHX. (edu.au)
CYP2D62
The major route of perhexiline metabolism in humans is hydroxylation by microsomal CYP2D6. (wikipedia.org)
The limited availability of CYP2D6 means perhexiline metabolism is a saturable process. (wikipedia.org)
Toxicity1
The risk of perhexiline toxicity is reduced by therapeutic drug monitoring (TDM). (wikipedia.org)
The Antianginal Drug Perhexiline Displays Cytotoxicity against Colorectal Cancer Cells In Vitro: A Potential for Drug Repurposing. (edu.au)
Inhibitor1
However, perhexiline, a non-rapalog mTORC1 inhibitor, was synergistic with PHGDH inhibition and able to cause cell death in osteosarcoma cells. (wustl.edu)
Exercise1
The purpose of this study is to evaluate the effect of perhexiline on exercise performance (efficacy) and safety in patients with hypertrophic cardiomyopathy and moderate-to-severe heart failure following dosing for 16 weeks. (stanfordhealthcare.org)
Amiodarone2
Drugs rarely cause steatohepatitis, but amiodarone, perhexiline, and DH, have unequivocally been found to independently induce the histologic picture of alcoholic liver disease or NASH. (nih.gov)
The adverse effects of perhexiline have been seen in more than 60% of recipients in some clinical trials. (wikipedia.org)
In the clinical setting, cytochrome P450 (CYP) 2D6 is considered as a possible risk factor for the adverse effects of perhexiline. (bvsalud.org)
Angina4
In this study we have demonstrated the efficacy and safety of perhexiline therapy which is the only metabolic agent currently in clinical use in the UK for CHF and refractory angina. (medscape.com)
This study, to date, represents the longest reported follow-up ever of patients with CHF and/or refractory angina treated with perhexiline. (medscape.com)
c) An independent predictor of response to perhexiline is the presence of refractory angina. (medscape.com)
[ 23 ] In addition to being excellent in chronic stable angina, perhexiline is also an effective therapy in acute coronary syndrome. (medscape.com)
Perhexiline (Pexsig) is a prophylactic antianginal agent used primarily in Australia and New Zealand. (wikipedia.org)
Perhexiline is a prophylactic antianginal agent developed in the 1970s. (bvsalud.org)
Mitochondrial3
Perhexiline is thought to act by inhibiting mitochondrial carnitine palmitoyltransferase-1. (wikipedia.org)
[ 15 ] Perhexiline inhibits both carnitine palmitoyl transferase-1 (CPT-1) and CPT-2, which are involved in mitochondrial uptake of long-chain fatty acids. (medscape.com)
Furthermore, perhexiline-induced mitochondrial damage, apoptosis, and ER stress were also attenuated in CYP2D6-overexpressing HepG2 cells. (bvsalud.org)
Symptomatic3
Perhexiline therapy provides symptomatic relief in the majority of patients with minimal side effects or toxicity. (medscape.com)
Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. (ox.ac.uk)
CONCLUSIONS: In symptomatic hypertrophic cardiomyopathy, perhexiline, a modulator of substrate metabolism, ameliorates cardiac energetic impairment, corrects diastolic dysfunction, and increases exercise capacity. (ox.ac.uk)
Metabolic2
[ 18 ] These observations provided the theoretical platform for the use of metabolic modulators such as perhexiline in CHF and coronary artery disease. (medscape.com)
We hypothesized that the metabolic modulator perhexiline would ameliorate myocardial energy deficiency and thereby improve diastolic function and exercise capacity. (ox.ac.uk)
Metabolism5
The major route of perhexiline metabolism in humans is hydroxylation by microsomal CYP2D6. (wikipedia.org)
The limited availability of CYP2D6 means perhexiline metabolism is a saturable process. (wikipedia.org)
However, the role of CYP-mediated metabolism in the toxicity of perhexiline, particularly in the intact cells, remains unclear. (bvsalud.org)
We also determined that CYP1A2, 2C19, and 3A4 contribute to the metabolism of perhexiline. (bvsalud.org)
These findings suggest that CYP2D6-mediated metabolism protects the cells from perhexiline-induced cytotoxicity and support the clinical observation that CYP2D6 poor metabolizers may have higher risk for perhexiline-induced hepatotoxicity. (bvsalud.org)
Assay1
Application of an improved HPLC perhexiline assay to human plasma specimens. (wikipedia.org)
Myocardial1
Perhexiline works by modifying myocardial substrate utilization from free fatty acids (FFAs) to carbohydrates. (medscape.com)
Ratios1
There is a segment of the population with very low hydroxyperhexiline/perhexiline ratios, this subpopulation contains those patients with the PM phenotype. (wikipedia.org)
Inhibits1
18. Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth. (nih.gov)
Concentration1
therefore, the Cis-hydroxyperhexiline/perhexiline concentration ratio may be useful for optimizing individual patient treatment with the antianginal agent perhexiline. (wikipedia.org)
Drugs2
Above on perhexiline and thiopurines will not be to suggest that customized medicine with drugs metabolized by several pathways will under no circumstances be attainable. (dna-pkinhibitor.com)
In cl.Above on perhexiline and thiopurines is just not to suggest that personalized medicine with drugs metabolized by many pathways will never ever be achievable. (dna-pkinhibitor.com)
Patients4
The principal findings are: (a) a majority of patients experienced symptom relief with perhexiline therapy. (medscape.com)
b) The use of perhexiline in patients was safe and only a small minority developed any side effects or abnormal LFTs. (medscape.com)
In a systematic review of 26 randomized, double-blind, controlled trials including about 700 patients, perhexiline was found to be extremely potent at providing symptom relief as a monotherapy or as an adjunct to current best anti-anginal therapy. (medscape.com)
Recently, our group have demonstrated the beneficial short-term effects of perhexiline in patients with CHF (ischaemics and non-ischaemics) in a double-blind, randomized, placebo-controlled trial. (medscape.com)
Method1
Prof. M.F. has applied for a method of use patent for perhexiline. (medscape.com)