PERHEXILINE MALEATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H35N.C4H4O4
Molecular Weight	393.5601
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.C(C(C1CCCCC1)C2CCCCC2)C3CCCCN3

InChI

InChIKey=JDZOTSLZMQDFLG-BTJKTKAUSA-N

InChI=1S/C19H35N.C4H4O4/c1-3-9-16(10-4-1)19(17-11-5-2-6-12-17)15-18-13-7-8-14-20-18;5-3(6)1-2-4(7)8/h16-20H,1-15H2;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C19H35N
Molecular Weight	277.4879
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 8297	77.0 µM [IC50]
Carnitine palmitoyltransferase 1B 5 Target ID: CHEMBL3216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8694852	Inhibitor 8297	148.0 µM [IC50]
HERG 92 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10369479 \| https://www.ncbi.nlm.nih.gov/pubmed/18701618	Blocker 537	7.8 µM [IC50]
Voltage-gated potassium channel subunit Kv1.5 37 Target ID: CHEMBL4306 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7616429	Blocker 537	1.5 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Angina pectoris 106 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17445089	Primary	Approved 8429	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 1132	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
[The classic anti-anginal agents and molsidomine].	1983 Feb	6407452
Drugs and steatohepatitis.	2002	12016549
Leustroducsin B activates nuclear factor-kappaB via the acidic sphingomyelinase pathway in human bone marrow-derived stromal cell line KM-102.	2002 Mar	12034042
The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure.	2002 Nov	12439634
A new hepatoma cell line for toxicity testing at repeated doses.	2003 Apr	12776925
Polymorphic hydroxylation of perhexiline in vitro.	2003 Jun	12814462
The metabolic "switch" AMPK regulates cardiac heparin-releasable lipoprotein lipase.	2005 Jan	15328075
Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes.	2005 Oct 14	16126172
Searching for new antimalarial therapeutics amongst known drugs.	2006 Jun	16882315
Effects of perhexiline and nitroglycerin on vascular, neutrophil and platelet function in patients with stable angina pectoris.	2007 Mar 29	17292880
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
Metabolic agents in the management of diabetic coronary patients: a new era.	2008 Jun 23	17561287
Steatohepatitis-inducing drugs trigger cytokeratin cross-links in hepatocytes. Possible contribution to Mallory-Denk body formation.	2008 Sep	18603402
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
Stereoselective Inhibition of the hERG1 Potassium Channel.	2010	21833176
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
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

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 `Fri Dec 15 15:26:35 UTC 2023` Edited by `admin` on `Fri Dec 15 15:26:35 UTC 2023`
Record UNII	K7V8Y90G0H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PERHEXILINE MALEATE

Official Name

English

PERHEXILINUM

Common Name

English

2-(2,2-DICYCLOHEXYLETHYL)PIPERIDINE MALEATE

Systematic Name

English

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

Systematic Name

English

Perhexiline maleate [WHO-DD]

Common Name

English

PERHEXILINUM [HPUS]

Common Name

English

PERHEXILINE MALEATE [MI]

Common Name

English

NSC-758409

Code

English

PIPERIDINE, 2-(2,2-DICYCLOHEXYLETHYL)-, MALEATE (1:1)

Systematic Name

English

PERHEXILINE MALEATE [USAN]

Common Name

English

PERHEXILINE MALEATE [MART.]

Common Name

English

PIPERIDINE, 2-(2,2-DICYCLOHEXYLETHYL)-, (2Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

PIPERIDINE, 2-(2,2-DICYCLOHEXYLETHYL)-, (Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

PEXID

Brand Name

English

2-(2,2-Dicyclohexylethyl)piperidine maleate (1:1)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C333