Basic information
- CAS
35193-73-8- Standard SMILES
C1CCC(C(CC2CCCCN2)C2CCCCC2)CC1- InChIKey
CYXKNKQEMFBLER-UHFFFAOYSA-N- Molecular formula
- C19H35N
- Average molar mass
- 277.5 g/mol
- Monoisotopic mass
- 277.27695012
Overview
Perhexiline is a member of piperidines. It has a role as a cardiovascular drug.
Names & identifiers
- Preferred name
- Perhexiline
- IUPAC
- 2-(2,2-dicyclohexylethyl)piperidine
- English name
- perhexiline
- Molecular formula
- C19H35N
- Molecular weight
- 277.49
Names & synonyms
PERHEXILINE2-(2,2-Dicyclohexylethyl)piperidinePerhexilene6621-47-2PerhexilinaPiperidine, 2-(2,2-dicyclohexylethyl)-PerhexilinumDTXSID7023439KU65374X44CHEBI:35553RefChem:860305DTXCID603439
Show more names
PerhexillinePerhexiline USP/EP/BPPerhexiline (Mixture of Diastereomers)(S)-2-(2,2-Dicyclohexylethyl)piperidine(R)-2-(2,2-Dicyclohexylethyl)piperidine(2S)-2-(2,2-Dicyclohexylethyl)piperidine(2R)-2-(2,2-Dicyclohexylethyl)piperidine
C08EX02229-569-5Perhexilinum [INN-Latin]Perhexilina [INN-Spanish](+)-2-(2,2-Dicyclohexylethyl)piperidine(-)-2-(2,2-Dicyclohexylethyl)piperidine39648-48-1Perhexiline (INN)
Database identifiers
- CAS
35193-73-8、39648-47-0、39648-48-1、6621-47-2- PubChem CID
- 4746
- DTXSID
DTXSID7023439- ChEMBL
Properties
Computed structural properties
- XLogP
- 6.8
- Topological polar surface area
- 12 Ų
- Hydrogen bond donors
- 1
- Hydrogen bond acceptors
- 1
- Rotatable bonds
- 4
- Heavy atoms
- 20
- Formal charge
- 0
- Complexity
- 245
Experimental & physicochemical properties
LogP6.2
Solubility2.72e-05 g/L
Physical DescriptionSolid
Collision Cross Section179.09 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
Physicochemical properties
- Boiling point
- 340 · 340.0±10.0 °C(Predicted)
- Density
- 0.926 · 0.926±0.06 g/cm3(Predicted)
- pka
- 10.36 · pKa 10.36 ± 0.06(40% EtOH,t =25,) (Uncertain)
- FDA UNII
- 65374 X44 · KU65374X44
- ATC code
- 8 EX02 · C08EX02
Safety & regulation
Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.
Toxicology
Exposure RoutesWell absorbed (>80%) from the gastrointestinal tract following oral administration.
Toxicity Summary
Perhexiline binds to the mitochondrial enzyme carnitine palmitoyltransferase (CPT)-1 and CPT-2. It acts by shifting myocardial substrate utilisation from long chain fatty acids to carbohydrates through inhibition of CPT-1 and, to a lesser extent, CPT-2, resulting in increased glucose and lactate utilization. This results in increased ATP production for the same O2 consumption as before and consequently increases myocardial efficiency.
Signs and SymptomsShort term adverse effects include nausea, transient dizziness, hypoglycaemia in diabetic patients, and torsade de pointes (rare).
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury
Drug Induced Liver Injury Rank (DILIrank 2.0)
Perhexiline
vMost-DILI-concern
8
Withdrawn
DOI:10.1016/j.drudis.2016.02.015
Toxicity DataLD50: 2150 mg/kg (Oral, Rat) (A308)
LD50: 2641 mg/kg (Oral, Mouse) (A308)
Chemistry & industry
Pharmacology
ATC Code
C - Cardiovascular system
QC - Cardiovascular system
Protein BindingPerhexiline and its metabolites are highly protein bound (>90%).
Pharmacodynamics
Used in the treatment of unresponsive or refractory angina. Perhexiline increases glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Perhexiline also potentiates platelet responsiveness to nitric oxide both in patients with angina and patients with acute coronary syndrome. The predominant mechanism of this particular perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for nitric oxide clearance by neutrophil-derived oxygen. Perhexiline relieves symptoms of angina, improves exercise tolerance, and increases the workload needed to induce ischaemia when used as monotherapy. The primary therapeutic roles for perhexiline are as short-term therapy (less than 3 months duration) in patients with severe ischaemia awaiting coronary revascularisation or long-term therapy in patients with ischaemic symptoms refractory to other therapeutic measures.
Mechanism of Action
Perhexiline binds to the mitochondrial enzyme carnitine palmitoyltransferase (CPT)-1 and CPT-2. It acts by shifting myocardial substrate utilisation from long chain fatty acids to carbohydrates through inhibition of CPT-1 and, to a lesser extent, CPT-2, resulting in increased glucose and lactate utilization. This results in increased ATP production for the same O2 consumption as before and consequently increases myocardial efficiency.
Biological Half-LifeVariable and non-linear. Some reports show a half-life of 2-6 days, others indicate it could be as high as 30 days.
Metabolism/Metabolites
The principal metabolites of perhexiline in man are monohydroxyperhexiline (which is excreted, in part, conjugated with glucuronic acid) and dihydroxyperhexiline that accounts for a relatively small proportion of the total metabolites. Two unidentified metabolites have also been found in the faeces. The pharmacological activity of the metabolites is not known. Hydroxylation of perhexiline is controlled by cytochrome P450 2D6 (CY P450 2D6).
Related reactions
2 records
Compound notes
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