PERHEXILINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H35N
Molecular Weight	277.4886
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CCC(CC1)C(CC2CCCCN2)C3CCCCC3

InChI

InChIKey=CYXKNKQEMFBLER-UHFFFAOYSA-N

InChI=1S/C19H35N/c1-3-9-16(10-4-1)19(17-11-5-2-6-12-17)15-18-13-7-8-14-20-18/h16-20H,1-15H2

HIDE SMILES / InChI

Molecular Formula	C19H35N
Molecular Weight	277.4886
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17445089 | http://www.medsafe.govt.nz/profs/Datasheet/p/pexsigtab.pdf | http://adisinsight.springer.com/drugs/800037277

Perhexiline, 2-(2,2-dicyclohexylethyl)piperidine, is an anti-anginal drug. Perhexiline reduces fatty acid metabolism through the inhibition of carnitine palmitoyltransferase, the enzyme responsible for mitochondrial uptake of long-chain fatty acids. Perhexiline is used for reducing the frequency of moderate to severe attacks of angina pectoris due to coronary artery disease in patients who have not responded to other conventional therapy or in whom such therapy may be contraindicated. Heart Metabolics Limited is developing perhexiline for the treatment of hypertrophic cardiomyopathy

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Carnitine palmitoyltransferase 1A 5 Target ID: CHEMBL3858 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8694852	Inhibitor 7728	77.0 µM [IC50]
Carnitine palmitoyltransferase 1B 5 Target ID: CHEMBL3216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8694852	Inhibitor 7728	148.0 µM [IC50]
HERG 89 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10369479 \| https://www.ncbi.nlm.nih.gov/pubmed/18701618	Blocker 511	7.8 µM [IC50]
Voltage-gated potassium channel subunit Kv1.5 36 Target ID: CHEMBL4306 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7616429	Blocker 511	1.5 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Angina pectoris 88 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17445089	Primary	Approved 8043	PEXSIG Approved Use To reduce the frequency of moderate to severe attacks of angina pectoris due to coronary artery disease in patients who have not responded to other conventional therapy or in whom such therapy may be contraindicated. Launch Date 2.52374401E11
Hypertrophic cardiomyopathy 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20921436	Primary	Phase II 1101	Unknown Approved Use Unknown
Schistosomiasis 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27518281	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
[Electrophysiological study of latent neuropathies induced by perhexiline].	1978 Nov	81769
[The classic anti-anginal agents and molsidomine].	1983 Feb	6407452
Perhexilene neuropathy: a report of two cases.	1984 Jun	6093756
Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.	1985 Sep-Oct	4029887
Impaired tissue responsiveness to organic nitrates and nitric oxide: a new therapeutic frontier?	2007 Nov	17765975
In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies.	2007 Sep	17567588
Metabolic therapy of heart failure.	2008	18991675
Modulation of cardiac metabolism during myocardial ischemia.	2008	18991673
The pathophysiology of heart failure: a tale of two old paradigms revisited.	2008 Apr	18478870
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.	2008 Dec	18493746
Management of the metabolic syndrome in cardiovascular disease.	2008 Feb	18325305
Overview of emerging pharmacologic agents for acute heart failure syndromes.	2008 Feb	18279775
Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.	2008 Feb	18224312
Phospholipidosis assay in HepG2 cells and rat or rhesus hepatocytes using phospholipid probe NBD-PE.	2008 Jun	18537465
Gene expression profiling in rat liver treated with compounds inducing phospholipidosis.	2008 Jun 15	18355885
Metabolic agents in the management of diabetic coronary patients: a new era.	2008 Jun 23	18199501
Metabolic agents in the management of diabetic coronary patients: a new era.	2008 Jun 23	17561287
Steady-state pharmacokinetics of the enantiomers of perhexiline in CYP2D6 poor and extensive metabolizers administered Rac-perhexiline.	2008 Mar	17875193
Drug binding to the inactivated state is necessary but not sufficient for high-affinity binding to human ether-à-go-go-related gene channels.	2008 Nov	18701618
Chronic stable angina pectoris.	2008 Sep	18725007
Steatohepatitis-inducing drugs trigger cytokeratin cross-links in hepatocytes. Possible contribution to Mallory-Denk body formation.	2008 Sep	18603402
Ca2+-dependent functions in peptidoglycan-stimulated mouse dendritic cells.	2009	19710531
Effects of metabolic approach in diabetic patients with coronary artery disease.	2009	19275650
The metabolic treatment of coronary artery disease and heart failure.	2009	19275645
Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond.	2009 Dec	19876734
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.	2009 Dec 2	19956587
Overview of therapeutic drug monitoring.	2009 Mar	19270474
Effect of intracellular lipid droplets on cytosolic Ca2+ and cell death during ischaemia-reperfusion injury in cardiomyocytes.	2009 Mar 15	19188253
Diabetic cardiomyopathy.	2009 May	19364331
Relationship between in vitro phospholipidosis assay using HepG2 cells and 2-week toxicity studies in rats.	2009 Oct	19793005
Determination of perhexiline and its metabolite hydroxyperhexiline in human plasma by liquid chromatography/tandem mass spectrometry.	2009 Oct 1	19646935
The adrenergic-fatty acid load in heart failure.	2009 Oct 27	19850204
Multi-centre experience on the use of perhexiline in chronic heart failure and refractory angina: old drug, new hope.	2009 Sep	19656806
Multiplexed assay panel of cytotoxicity in HK-2 cells for detection of renal proximal tubule injury potential of compounds.	2009 Sep	19523510
Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling.	2009 Sep 22	19771169
Stereoselective Inhibition of the hERG1 Potassium Channel.	2010	21833176
Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases.	2010 Apr 9	20147746
A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs.	2010 Aug	21304177
Niclosamide prevents the formation of large ubiquitin-containing aggregates caused by proteasome inhibition.	2010 Dec 23	21203451
The pathophysiology of diastolic heart failure.	2010 Feb 24	20948816
Modulation of myocardial metabolism: an emerging therapeutic principle.	2010 Jul	20535068
Metabolic Fingerprinting in Toxicological Assessment Using FT-ICR MS.	2010 Jun	22272014
Effects of perhexiline on myocardial deformation in patients with ischaemic left ventricular dysfunction.	2010 Mar 4	19840889
Lack of effect of perhexiline in ischaemic heart failure.	2010 Mar 4	19748138
Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure.	2010 Nov 16	21080957
Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy.	2010 Oct 19	20921440
Perhexiline and hypertrophic cardiomyopathy: a new horizon for metabolic modulation.	2010 Oct 19	20921436
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
Comparison of a genomic and a multiplex cell imaging approach for the detection of phospholipidosis.	2011 Oct	21515356
A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis.	2013 Feb	23243064

Patents

Sample Use Guides

In Vivo Use Guide

Commence therapy with 100mg daily. Adjust progressively, up or down, at 2 to 4 weekly intervals based on the results of plasma level monitoring. It is generally advised not to administer more than 300mg per day, in divided doses, but in certain cases it may be necessary to use 400mg per day. The maintenance dose must be the minimum dose that is effective and well tolerated.

Route of Administration: Oral

In Vitro Use Guide

Perhexiline maleate was more potent on basal LH release from rat anterior pituitary cell aggregates than on LH stimulated by LHRH. The increases of basal LH secretion induced by perhexiline maleate were 69% (p < 0.001) at a concentration of 10(-7)M, 130% (p < 0.001) at a concentration of 10(-5)M and 250% (p < 0.001) at a concentration of 10(-4)M. Perhexiline maleate also increased the LHRH-stimulated LH release by 25.5% (p < 0.05) at a concentration of 10(-5)M and by 74.5% (p < 0.01) at the concentration of 10(-4)M.

Substance Class	Chemical Created by `admin` on `Sat Jun 26 14:35:09 UTC 2021` Edited by `admin` on `Sat Jun 26 14:35:09 UTC 2021`
Record UNII	KU65374X44
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PERHEXILINE

Official Name

English

2-(2,2-DICYCLOHEXYLETHYL)PIPERIDINE

Systematic Name

English

PERHEXILINE [WHO-DD]

Common Name

English

(+/-)-2-(2,2-DICYCLOHEXYLETHYL)PIPERIDINE

Systematic Name

English

PERHEXILINE [INN]

Common Name

English

PERHEXILINE [MI]

Common Name

English

PIPERIDINE, 2-(2,2-DICYCLOHEXYLETHYL)-

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

C08EX02