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Identification
NamePerhexiline
Accession NumberDB01074  (APRD00107)
TypeSmall Molecule
GroupsApproved
Description2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. [PubChem]
Structure
Thumb
Synonyms
(-)-2-(2,2-Dicyclohexylethyl)piperidine
(+)-2-(2,2-Dicyclohexylethyl)piperidine
2-(2,2-Dicyclohexylethyl)piperidine
Perhexilene
Perhexilina
Perhexiline
Perhexilinum
Perhexilline
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIKU65374X44
CAS number6621-47-2
WeightAverage: 277.4879
Monoisotopic: 277.276950125
Chemical FormulaC19H35N
InChI KeyCYXKNKQEMFBLER-UHFFFAOYSA-N
InChI
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
IUPAC Name
2-(2,2-dicyclohexylethyl)piperidine
SMILES
C(C(C1CCCCC1)C1CCCCC1)C1CCCCN1
Pharmacology
IndicationFor the management of severe angina pectoris.
Structured Indications Not Available
PharmacodynamicsUsed 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 actionPerhexiline 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Carnitine O-palmitoyltransferase 1, liver isoformProteinyes
inhibitor
HumanP50416 details
Carnitine O-palmitoyltransferase 2, mitochondrialProteinyes
inhibitor
HumanP23786 details
Related Articles
AbsorptionWell absorbed (>80%) from the gastrointestinal tract following oral administration.
Volume of distributionNot Available
Protein bindingPerhexiline and its metabolites are highly protein bound (>90%).
Metabolism

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).

SubstrateEnzymesProduct
Perhexiline
Not Available
cis-Hydroxy PerhexilineDetails
Perhexiline
Not Available
MonohydroxyperhexilineDetails
Route of eliminationNot Available
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.
ClearanceNot Available
ToxicityOral LD50 rat: 2150 mg/kg; Oral LD50 Mouse: 2641 mg/kg. Short term adverse effects include nausea, transient dizziness, hypoglycaemia in diabetic patients, and torsade de pointes (rare).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
2-HYDROXY-1,4-NAPHTHOQUINONEThe risk or severity of adverse effects can be increased when 2-HYDROXY-1,4-NAPHTHOQUINONE is combined with Perhexiline.Experimental
2-mercaptobenzothiazoleThe risk or severity of adverse effects can be increased when 2-mercaptobenzothiazole is combined with Perhexiline.Vet Approved
AbirateroneThe serum concentration of Perhexiline can be increased when it is combined with Abiraterone.Approved
AlfuzosinAlfuzosin may increase the hypotensive activities of Perhexiline.Approved, Investigational
AmiodaroneThe metabolism of Perhexiline can be decreased when combined with Amiodarone.Approved, Investigational
AmobarbitalThe metabolism of Perhexiline can be increased when combined with Amobarbital.Approved, Illicit
AmorolfineThe risk or severity of adverse effects can be increased when Amorolfine is combined with Perhexiline.Approved
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Perhexiline.Approved, Investigational
AN2690The risk or severity of adverse effects can be increased when AN2690 is combined with Perhexiline.Investigational
AnidulafunginThe risk or severity of adverse effects can be increased when Anidulafungin is combined with Perhexiline.Approved, Investigational
AprepitantThe serum concentration of Perhexiline can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Perhexiline.Approved
AtazanavirThe metabolism of Perhexiline can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Perhexiline can be decreased when combined with Atomoxetine.Approved
AtosibanThe risk or severity of adverse effects can be increased when Perhexiline is combined with Atosiban.Approved
Atracurium besylatePerhexiline may increase the neuromuscular blocking activities of Atracurium besylate.Approved
Bafilomycin A1The risk or severity of adverse effects can be increased when Bafilomycin A1 is combined with Perhexiline.Experimental
BarbexacloneThe metabolism of Perhexiline can be increased when combined with Barbexaclone.Experimental
BarbitalThe metabolism of Perhexiline can be increased when combined with Barbital.Illicit
Benzoic AcidThe risk or severity of adverse effects can be increased when Benzoic Acid is combined with Perhexiline.Approved
BetaxololThe metabolism of Perhexiline can be decreased when combined with Betaxolol.Approved
BexaroteneThe serum concentration of Perhexiline can be decreased when it is combined with Bexarotene.Approved, Investigational
BifonazoleThe risk or severity of adverse effects can be increased when Bifonazole is combined with Perhexiline.Approved
BoceprevirThe metabolism of Perhexiline can be decreased when combined with Boceprevir.Approved
BortezomibThe metabolism of Perhexiline can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Perhexiline can be decreased when it is combined with Bosentan.Approved, Investigational
BucindololBucindolol may increase the hypotensive activities of Perhexiline.Investigational
BupropionThe metabolism of Perhexiline can be decreased when combined with Bupropion.Approved
ButenafineThe risk or severity of adverse effects can be increased when Butenafine is combined with Perhexiline.Approved
ButoconazoleThe risk or severity of adverse effects can be increased when Butoconazole is combined with Perhexiline.Approved
CalciumThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Calcium.Nutraceutical
Calcium AcetateThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Calcium Acetate.Approved
Calcium carbonateThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Calcium carbonate.Approved
Calcium ChlorideThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Calcium Chloride.Approved
Calcium citrateThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Calcium citrate.Approved
Calcium glubionateThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Calcium glubionate.Approved
Calcium GluceptateThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Calcium Gluceptate.Approved
Calcium gluconateThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Calcium gluconate.Approved, Vet Approved
CandicidinThe risk or severity of adverse effects can be increased when Candicidin is combined with Perhexiline.Withdrawn
CarbamazepineThe metabolism of Perhexiline can be increased when combined with Carbamazepine.Approved, Investigational
CarbomycinThe metabolism of Perhexiline can be decreased when combined with Carbomycin.Vet Approved
CarvedilolCarvedilol may increase the hypotensive activities of Perhexiline.Approved, Investigational
CaspofunginThe risk or severity of adverse effects can be increased when Caspofungin is combined with Perhexiline.Approved
CelecoxibThe metabolism of Perhexiline can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Perhexiline can be increased when it is combined with Ceritinib.Approved
CeruleninThe risk or severity of adverse effects can be increased when Cerulenin is combined with Perhexiline.Approved
ChloroquineThe metabolism of Perhexiline can be decreased when combined with Chloroquine.Approved, Vet Approved
ChloroxineThe risk or severity of adverse effects can be increased when Chloroxine is combined with Perhexiline.Approved
ChlorpromazineThe metabolism of Perhexiline can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Perhexiline can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CiclopiroxThe risk or severity of adverse effects can be increased when Ciclopirox is combined with Perhexiline.Approved, Investigational
CimetidineThe serum concentration of Perhexiline can be increased when it is combined with Cimetidine.Approved
CinacalcetThe metabolism of Perhexiline can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Perhexiline can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Perhexiline can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Perhexiline can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Perhexiline can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Perhexiline can be decreased when combined with Clomipramine.Approved, Vet Approved
ClopidogrelThe therapeutic efficacy of Clopidogrel can be decreased when used in combination with Perhexiline.Approved, Nutraceutical
ClotrimazoleThe risk or severity of adverse effects can be increased when Clotrimazole is combined with Perhexiline.Approved, Vet Approved
ClozapineThe metabolism of Perhexiline can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Perhexiline can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Perhexiline can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Perhexiline can be increased when it is combined with Conivaptan.Approved, Investigational
CordycepinThe risk or severity of adverse effects can be increased when Cordycepin is combined with Perhexiline.Investigational
CrizotinibThe metabolism of Perhexiline can be decreased when combined with Crizotinib.Approved
CyclosporineThe risk or severity of adverse effects can be increased when Cyclosporine is combined with Perhexiline.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Perhexiline can be decreased when it is combined with Dabrafenib.Approved
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Perhexiline.Investigational
DarifenacinThe metabolism of Perhexiline can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Perhexiline can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Perhexiline can be increased when it is combined with Dasatinib.Approved, Investigational
Decanoic AcidThe risk or severity of adverse effects can be increased when Decanoic Acid is combined with Perhexiline.Experimental
DeferasiroxThe serum concentration of Perhexiline can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Perhexiline can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Perhexiline can be decreased when combined with Desipramine.Approved
DexamethasoneThe serum concentration of Perhexiline can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DihydroergotamineThe metabolism of Perhexiline can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Perhexiline can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Perhexiline can be decreased when combined with Diphenhydramine.Approved
DoxazosinDoxazosin may increase the hypotensive activities of Perhexiline.Approved
DoxorubicinThe metabolism of Perhexiline can be decreased when combined with Doxorubicin.Approved, Investigational
DoxycyclineThe metabolism of Perhexiline can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Perhexiline can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Perhexiline can be decreased when combined with Duloxetine.Approved
EconazoleThe risk or severity of adverse effects can be increased when Econazole is combined with Perhexiline.Approved
EfavirenzThe serum concentration of Perhexiline can be decreased when it is combined with Efavirenz.Approved, Investigational
EfinaconazoleThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Perhexiline.Approved
EliglustatThe metabolism of Perhexiline can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Perhexiline can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Perhexiline can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Perhexiline can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Perhexiline can be decreased when it is combined with Etravirine.Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Perhexiline.Approved
FluconazoleThe serum concentration of Perhexiline can be increased when it is combined with Fluconazole.Approved
FlucytosineThe risk or severity of adverse effects can be increased when Flucytosine is combined with Perhexiline.Approved
FluoxetineThe metabolism of Perhexiline can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Perhexiline can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Perhexiline can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Perhexiline can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Perhexiline.Approved
Fusidic AcidThe serum concentration of Perhexiline can be increased when it is combined with Fusidic Acid.Approved
GlyphosateThe risk or severity of adverse effects can be increased when Glyphosate is combined with Perhexiline.Experimental
GriseofulvinThe risk or severity of adverse effects can be increased when Griseofulvin is combined with Perhexiline.Approved, Vet Approved
HaloperidolThe metabolism of Perhexiline can be decreased when combined with Haloperidol.Approved
HaloproginThe risk or severity of adverse effects can be increased when Haloprogin is combined with Perhexiline.Approved, Withdrawn
HexetidineThe risk or severity of adverse effects can be increased when Hexetidine is combined with Perhexiline.Approved
HexobarbitalThe metabolism of Perhexiline can be increased when combined with Hexobarbital.Approved
IdelalisibThe serum concentration of Perhexiline can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Perhexiline can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Perhexiline can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Perhexiline can be decreased when combined with Indinavir.Approved
IndoraminIndoramin may increase the hypotensive activities of Perhexiline.Withdrawn
IsavuconazoniumThe metabolism of Perhexiline can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoconazoleThe risk or severity of adverse effects can be increased when Isoconazole is combined with Perhexiline.Approved
IsoniazidThe metabolism of Perhexiline can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Perhexiline can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Perhexiline can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Perhexiline can be increased when it is combined with Ivacaftor.Approved
JosamycinThe metabolism of Perhexiline can be decreased when combined with Josamycin.Approved
KetoconazoleThe metabolism of Perhexiline can be decreased when combined with Ketoconazole.Approved, Investigational
KitasamycinThe metabolism of Perhexiline can be decreased when combined with Kitasamycin.Experimental
LabetalolLabetalol may increase the hypotensive activities of Perhexiline.Approved
LopinavirThe metabolism of Perhexiline can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Perhexiline can be decreased when combined with Lorcaserin.Approved
LovastatinThe metabolism of Perhexiline can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Perhexiline can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Perhexiline can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe metabolism of Perhexiline can be decreased when combined with Lumefantrine.Approved
Magnesium hydroxideThe risk or severity of adverse effects can be increased when Perhexiline is combined with Magnesium hydroxide.Approved
Magnesium oxideThe risk or severity of adverse effects can be increased when Perhexiline is combined with Magnesium oxide.Approved
Magnesium salicylateThe risk or severity of adverse effects can be increased when Perhexiline is combined with Magnesium salicylate.Approved
Magnesium SulfateThe risk or severity of adverse effects can be increased when Perhexiline is combined with Magnesium Sulfate.Approved, Vet Approved
MethadoneThe metabolism of Perhexiline can be decreased when combined with Methadone.Approved
MethohexitalThe metabolism of Perhexiline can be increased when combined with Methohexital.Approved
MethotrimeprazineThe metabolism of Perhexiline can be decreased when combined with Methotrimeprazine.Approved
MethylphenobarbitalThe metabolism of Perhexiline can be increased when combined with Methylphenobarbital.Approved
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Perhexiline.Approved, Investigational
MevastatinThe risk or severity of adverse effects can be increased when Mevastatin is combined with Perhexiline.Experimental
MicafunginThe risk or severity of adverse effects can be increased when Micafungin is combined with Perhexiline.Approved, Investigational
MiconazoleThe risk or severity of adverse effects can be increased when Miconazole is combined with Perhexiline.Approved, Investigational, Vet Approved
MifepristoneThe serum concentration of Perhexiline can be increased when it is combined with Mifepristone.Approved, Investigational
MiltefosineThe risk or severity of adverse effects can be increased when Miltefosine is combined with Perhexiline.Approved
MirabegronThe metabolism of Perhexiline can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Perhexiline can be decreased when it is combined with Mitotane.Approved
MivacuriumPerhexiline may increase the neuromuscular blocking activities of Mivacurium.Approved
ModafinilThe serum concentration of Perhexiline can be decreased when it is combined with Modafinil.Approved, Investigational
MonensinThe risk or severity of adverse effects can be increased when Monensin is combined with Perhexiline.Vet Approved
MyxothiazolThe risk or severity of adverse effects can be increased when Myxothiazol is combined with Perhexiline.Experimental
NafcillinThe metabolism of Perhexiline can be increased when combined with Nafcillin.Approved
NaftifineThe risk or severity of adverse effects can be increased when Naftifine is combined with Perhexiline.Approved
NatamycinThe risk or severity of adverse effects can be increased when Natamycin is combined with Perhexiline.Approved
NefazodoneThe metabolism of Perhexiline can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Perhexiline can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Perhexiline can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Perhexiline can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Perhexiline can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Perhexiline can be decreased when combined with Nilotinib.Approved, Investigational
NitroprussidePerhexiline may increase the hypotensive activities of Nitroprusside.Approved
NitroxolineThe risk or severity of adverse effects can be increased when Nitroxoline is combined with Perhexiline.Approved
NystatinThe risk or severity of adverse effects can be increased when Nystatin is combined with Perhexiline.Approved, Vet Approved
OlaparibThe metabolism of Perhexiline can be decreased when combined with Olaparib.Approved
OleandomycinThe metabolism of Perhexiline can be decreased when combined with Oleandomycin.Vet Approved
OsimertinibThe serum concentration of Perhexiline can be increased when it is combined with Osimertinib.Approved
OxiconazoleThe risk or severity of adverse effects can be increased when Oxiconazole is combined with Perhexiline.Approved
pafuramidineThe risk or severity of adverse effects can be increased when pafuramidine is combined with Perhexiline.Investigational
PalbociclibThe serum concentration of Perhexiline can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Perhexiline can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Perhexiline can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Perhexiline can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentamidineThe risk or severity of adverse effects can be increased when Pentamidine is combined with Perhexiline.Approved
PentobarbitalThe metabolism of Perhexiline can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Perhexiline can be increased when combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Perhexiline.Approved, Vet Approved
PosaconazoleThe metabolism of Perhexiline can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrazosinPrazosin may increase the hypotensive activities of Perhexiline.Approved
PrimidoneThe metabolism of Perhexiline can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Perhexiline can be decreased when combined with Promazine.Approved, Vet Approved
QuazepamThe serum concentration of Perhexiline can be increased when it is combined with Quazepam.Approved, Illicit
QuinidineThe metabolism of Perhexiline can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Perhexiline can be decreased when combined with Quinine.Approved
RadicicolThe risk or severity of adverse effects can be increased when Radicicol is combined with Perhexiline.Experimental
RanolazineThe metabolism of Perhexiline can be decreased when combined with Ranolazine.Approved, Investigational
RapacuroniumPerhexiline may increase the neuromuscular blocking activities of Rapacuronium.Withdrawn
RifabutinThe metabolism of Perhexiline can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Perhexiline can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Perhexiline can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Perhexiline can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Perhexiline can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Perhexiline can be decreased when combined with Ropinirole.Approved, Investigational
Salicylhydroxamic AcidThe risk or severity of adverse effects can be increased when Salicylhydroxamic Acid is combined with Perhexiline.Experimental
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Perhexiline.Approved, Vet Approved
SaquinavirThe metabolism of Perhexiline can be decreased when combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Perhexiline can be increased when combined with Secobarbital.Approved, Vet Approved
SertaconazoleThe risk or severity of adverse effects can be increased when Sertaconazole is combined with Perhexiline.Approved
SertralineThe metabolism of Perhexiline can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Perhexiline can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinSilodosin may increase the hypotensive activities of Perhexiline.Approved
SiltuximabThe serum concentration of Perhexiline can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Perhexiline can be increased when it is combined with Simeprevir.Approved
SinefunginThe risk or severity of adverse effects can be increased when Sinefungin is combined with Perhexiline.Experimental
SirolimusThe risk or severity of adverse effects can be increased when Sirolimus is combined with Perhexiline.Approved, Investigational
SolithromycinThe metabolism of Perhexiline can be decreased when combined with Solithromycin.Investigational
SorafenibThe metabolism of Perhexiline can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Perhexiline can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Perhexiline can be increased when it is combined with Stiripentol.Approved
SulconazoleThe risk or severity of adverse effects can be increased when Sulconazole is combined with Perhexiline.Approved
SulfisoxazoleThe metabolism of Perhexiline can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TamsulosinTamsulosin may increase the hypotensive activities of Perhexiline.Approved, Investigational
TavaboroleThe risk or severity of adverse effects can be increased when Tavaborole is combined with Perhexiline.Approved
TelaprevirThe metabolism of Perhexiline can be decreased when combined with Telaprevir.Approved
TelithromycinThe metabolism of Perhexiline can be decreased when combined with Telithromycin.Approved
TerazosinTerazosin may increase the hypotensive activities of Perhexiline.Approved
TerbinafineThe metabolism of Perhexiline can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TerconazoleThe risk or severity of adverse effects can be increased when Terconazole is combined with Perhexiline.Approved
ThiamylalThe metabolism of Perhexiline can be increased when combined with Thiamylal.Approved, Vet Approved
ThiopentalThe metabolism of Perhexiline can be increased when combined with Thiopental.Approved, Vet Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Perhexiline.Approved
ThiotepaThe metabolism of Perhexiline can be decreased when combined with Thiotepa.Approved
ThymolThe risk or severity of adverse effects can be increased when Thymol is combined with Perhexiline.Approved
TiclopidineThe metabolism of Perhexiline can be decreased when combined with Ticlopidine.Approved
TioconazoleThe risk or severity of adverse effects can be increased when Tioconazole is combined with Perhexiline.Approved
TipranavirThe metabolism of Perhexiline can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Perhexiline can be decreased when it is combined with Tocilizumab.Approved
TolnaftateThe risk or severity of adverse effects can be increased when Tolnaftate is combined with Perhexiline.Approved, Vet Approved
TranylcypromineThe metabolism of Perhexiline can be decreased when combined with Tranylcypromine.Approved
TrimazosinTrimazosin may increase the hypotensive activities of Perhexiline.Experimental
TrimetrexateThe risk or severity of adverse effects can be increased when Trimetrexate is combined with Perhexiline.Approved, Investigational
TroleandomycinThe metabolism of Perhexiline can be decreased when combined with Troleandomycin.Approved
TylosinThe metabolism of Perhexiline can be decreased when combined with Tylosin.Vet Approved
VenlafaxineThe metabolism of Perhexiline can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Perhexiline can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Perhexiline can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Perhexiline can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot Available
References
Synthesis Reference

Stephen W. Horgan, Frank P. Palopoli, Edward J. Schwoegler, “Process for preparing 2-(2,2-dicyclohexylethyl)piperidine.” U.S. Patent US4069222, issued August, 1950.

US4069222
General ReferencesNot Available
External Links
ATC CodesC08EX02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (25.6 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9818
Blood Brain Barrier+0.9796
Caco-2 permeable+0.6799
P-glycoprotein substrateNon-substrate0.5484
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8888
Renal organic cation transporterInhibitor0.6665
CYP450 2C9 substrateNon-substrate0.8539
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8779
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8452
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9548
BiodegradationNot ready biodegradable0.8346
Rat acute toxicity2.7630 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7559
hERG inhibition (predictor II)Non-inhibitor0.6082
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility0.0608 mg/LNot Available
logP6.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.72e-05 mg/mLALOGPS
logP5.87ALOGPS
logP5.53ChemAxon
logS-7ALOGPS
pKa (Strongest Basic)10.58ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity87.23 m3·mol-1ChemAxon
Polarizability36.22 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-001i-9000000000-e8335ba9964dd32ada29View in MoNA
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as piperidines. These are compounds containing a piperidine ring, which is a saturated aliphatic six-member ring with one nitrogen atom and five carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassNot Available
Direct ParentPiperidines
Alternative Parents
Substituents
  • Piperidine
  • Azacycle
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Carnitine o-palmitoyltransferase activity
Specific Function:
Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion. Plays an important role in triglyceride metabolism.
Gene Name:
CPT1A
Uniprot ID:
P50416
Molecular Weight:
88366.92 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Kennedy JA, Kiosoglous AJ, Murphy GA, Pelle MA, Horowitz JD: Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart. J Cardiovasc Pharmacol. 2000 Dec;36(6):794-801. [PubMed:11117381 ]
  4. Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD: Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005 Dec;46(6):849-55. [PubMed:16306812 ]
  5. Kennedy JA, Unger SA, Horowitz JD: Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem Pharmacol. 1996 Jul 26;52(2):273-80. [PubMed:8694852 ]
  6. Ashrafian H, Horowitz JD, Frenneaux MP: Perhexiline. Cardiovasc Drug Rev. 2007 Spring;25(1):76-97. [PubMed:17445089 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Carnitine o-palmitoyltransferase activity
Specific Function:
Not Available
Gene Name:
CPT2
Uniprot ID:
P23786
Molecular Weight:
73776.335 Da
References
  1. Kennedy JA, Kiosoglous AJ, Murphy GA, Pelle MA, Horowitz JD: Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart. J Cardiovasc Pharmacol. 2000 Dec;36(6):794-801. [PubMed:11117381 ]
  2. Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD: Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005 Dec;46(6):849-55. [PubMed:16306812 ]
  3. Kennedy JA, Unger SA, Horowitz JD: Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem Pharmacol. 1996 Jul 26;52(2):273-80. [PubMed:8694852 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23