Perhexiline
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Identification
- Generic Name
- Perhexiline
- DrugBank Accession Number
- DB01074
- Background
Perhexiline is a coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 277.4879
Monoisotopic: 277.276950125 - Chemical Formula
- C19H35N
- Synonyms
- Perhexilene
- Perhexilina
- Perhexiline
- Perhexilinum
Pharmacology
- Indication
For the management of severe angina pectoris.
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- 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.
Target Actions Organism ACarnitine O-palmitoyltransferase 1, liver isoform inhibitorHumans ACarnitine O-palmitoyltransferase 1, muscle isoform inhibitorHumans ACarnitine O-palmitoyltransferase 2, mitochondrial inhibitorHumans UVoltage-gated inwardly rectifying potassium channel KCNH2 Not Available Humans - Absorption
Well absorbed (>80%) from the gastrointestinal tract following oral administration.
- Volume of distribution
Not Available
- Protein binding
Perhexiline 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).
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- Route of elimination
Not Available
- Half-life
Variable and non-linear. Some reports show a half-life of 2-6 days, others indicate it could be as high as 30 days.
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Oral 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).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Perhexiline can be increased when it is combined with Abametapir. Abatacept The metabolism of Perhexiline can be increased when combined with Abatacept. Abiraterone The metabolism of Perhexiline can be decreased when combined with Abiraterone. Acarbose The risk or severity of hypoglycemia can be increased when Perhexiline is combined with Acarbose. Acebutolol Perhexiline may increase the arrhythmogenic activities of Acebutolol. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Perhexiline maleate K7V8Y90G0H 6724-53-4 JDZOTSLZMQDFLG-UHFFFAOYSA-N
Categories
- ATC Codes
- C08EX02 — Perhexiline
- Drug Categories
- Agents causing hyperkalemia
- Antiarrhythmic agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Membrane Transport Modulators
- Negative Inotrope
- Non-Selective Calcium Channel Blockers
- Piperidines
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Not Available
- Direct Parent
- Piperidines
- Alternative Parents
- Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Aliphatic heteromonocyclic compound / Amine / Azacycle / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound / Piperidine / Secondary aliphatic amine / Secondary amine
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- piperidines (CHEBI:35553)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- KU65374X44
- CAS number
- 6621-47-2
- InChI Key
- CYXKNKQEMFBLER-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
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 References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015207
- PubChem Compound
- 4746
- PubChem Substance
- 46504471
- ChemSpider
- 4584
- BindingDB
- 61402
- 8050
- ChEBI
- 35553
- ChEMBL
- CHEMBL75880
- Therapeutic Targets Database
- DAP000957
- PharmGKB
- PA130150436
- Wikipedia
- Perhexiline
- MSDS
- Download (25.6 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Withdrawn Treatment Hypertrophic Cardiomyopathy (HCM) 1 somestatus stop reason just information to hide 2 Completed Treatment Chronic Heart Failure (CHF) 1 somestatus stop reason just information to hide 2 Completed Treatment Heart Failure, Diastolic 1 somestatus stop reason just information to hide 2 Terminated Treatment Familial Hypertrophic Cardiomyopathy / Hypertrophic Cardiomyopathy (HCM) 1 somestatus stop reason just information to hide 2 Unknown Status Treatment Hypertrophic Cardiomyopathy (HCM) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 0.0608 mg/L Not Available logP 6.2 Not Available - Predicted Properties
Property Value Source Water Solubility 2.72e-05 mg/mL ALOGPS logP 5.87 ALOGPS logP 5.53 Chemaxon logS -7 ALOGPS pKa (Strongest Basic) 10.58 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 12.03 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 87.23 m3·mol-1 Chemaxon Polarizability 36.21 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9818 Blood Brain Barrier + 0.9796 Caco-2 permeable + 0.6799 P-glycoprotein substrate Non-substrate 0.5484 P-glycoprotein inhibitor I Non-inhibitor 0.8782 P-glycoprotein inhibitor II Non-inhibitor 0.8888 Renal organic cation transporter Inhibitor 0.6665 CYP450 2C9 substrate Non-substrate 0.8539 CYP450 2D6 substrate Substrate 0.8919 CYP450 3A4 substrate Non-substrate 0.7558 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8779 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8452 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.9548 Biodegradation Not ready biodegradable 0.8346 Rat acute toxicity 2.7630 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7559 hERG inhibition (predictor II) Non-inhibitor 0.6082
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 178.2902098 predictedDarkChem Lite v0.1.0 [M-H]- 165.67549 predictedDeepCCS 1.0 (2019) [M+H]+ 178.1033098 predictedDarkChem Lite v0.1.0 [M+H]+ 168.0335 predictedDeepCCS 1.0 (2019) [M+Na]+ 178.4953098 predictedDarkChem Lite v0.1.0 [M+Na]+ 174.12663 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 (PubMed:11350182, PubMed:14517221, PubMed:16651524, PubMed:9691089). Possesses also a lysine succinyltransferase activity that can regulate enzymatic activity of substrate proteins such as ENO1 and metabolism independent of its classical carnitine O-palmitoyltransferase activity (PubMed:29425493). Plays an important role in hepatic triglyceride metabolism (By similarity). Plays also a role in inducible regulatory T-cell (iTreg) differentiation once activated by butyryl-CoA that antagonizes malonyl-CoA-mediated CPT1A repression (By similarity). Sustains the IFN-I response by recruiting ZDHCC4 to palmitoylate MAVS at the mitochondria leading to MAVS stabilization and activation (PubMed:38016475). Promotes ROS-induced oxidative stress in liver injury via modulation of NFE2L2 and NLRP3-mediated signaling pathways (By similarity)
- Specific Function
- carnitine O-palmitoyltransferase activity
- Gene Name
- CPT1A
- Uniprot ID
- P50416
- Uniprot Name
- Carnitine O-palmitoyltransferase 1, liver isoform
- Molecular Weight
- 88366.92 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Ashrafian H, Horowitz JD, Frenneaux MP: Perhexiline. Cardiovasc Drug Rev. 2007 Spring;25(1):76-97. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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
- Specific Function
- carnitine O-palmitoyltransferase activity
- Gene Name
- CPT1B
- Uniprot ID
- Q92523
- Uniprot Name
- Carnitine O-palmitoyltransferase 1, muscle isoform
- Molecular Weight
- 87800.385 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites (PubMed:20538056, PubMed:24780397). Reconverts acylcarnitines back into the respective acyl-CoA esters that can then undergo beta-oxidation, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion. Active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters (PubMed:20538056)
- Specific Function
- acyltransferase activity
- Gene Name
- CPT2
- Uniprot ID
- P23786
- Uniprot Name
- Carnitine O-palmitoyltransferase 2, mitochondrial
- Molecular Weight
- 73776.335 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)
- Specific Function
- delayed rectifier potassium channel activity
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Voltage-gated inwardly rectifying potassium channel KCNH2
- Molecular Weight
- 126653.52 Da
References
- Perrin MJ, Kuchel PW, Campbell TJ, Vandenberg JI: Drug binding to the inactivated state is necessary but not sufficient for high-affinity binding to human ether-a-go-go-related gene channels. Mol Pharmacol. 2008 Nov;74(5):1443-52. doi: 10.1124/mol.108.049056. Epub 2008 Aug 13. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Davies BJ, Coller JK, Somogyi AA, Milne RW, Sallustio BC: CYP2B6, CYP2D6, and CYP3A4 catalyze the primary oxidative metabolism of perhexiline enantiomers by human liver microsomes. Drug Metab Dispos. 2007 Jan;35(1):128-38. doi: 10.1124/dmd.106.012252. Epub 2006 Oct 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Davies BJ, Coller JK, Somogyi AA, Milne RW, Sallustio BC: CYP2B6, CYP2D6, and CYP3A4 catalyze the primary oxidative metabolism of perhexiline enantiomers by human liver microsomes. Drug Metab Dispos. 2007 Jan;35(1):128-38. doi: 10.1124/dmd.106.012252. Epub 2006 Oct 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Davies BJ, Coller JK, Somogyi AA, Milne RW, Sallustio BC: CYP2B6, CYP2D6, and CYP3A4 catalyze the primary oxidative metabolism of perhexiline enantiomers by human liver microsomes. Drug Metab Dispos. 2007 Jan;35(1):128-38. doi: 10.1124/dmd.106.012252. Epub 2006 Oct 18. [Article]
- Davies BJ, Coller JK, James HM, Gillis D, Somogyi AA, Horowitz JD, Morris RG, Sallustio BC: Clinical inhibition of CYP2D6-catalysed metabolism by the antianginal agent perhexiline. Br J Clin Pharmacol. 2004 Apr;57(4):456-63. doi: 10.1046/j.1365-2125.2003.02033.x. [Article]
- Flockhart Table of Drug Interactions [Link]
Drug created at June 13, 2005 13:24 / Updated at October 03, 2024 04:26