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Identification
Name Methadone
Accession Number DB00333 (APRD00485)
Type small molecule
Groups approved
Description

A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Methadone is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3).

In Australia methadone is a Schedule 8 (controlled) drug.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
(+/-)-Methadone
(+/-)-Methadone hydrochloride
dl-Methadone
DL-Methadone hydrochloride
Methadon
Methadone HCL
Methadone hydrochloride
Phenadone hydrochloride
Salts Not Available
Brand names
Name Company
(+/-)-Tussal
Adanon
Adanon hydrochloride
Adolan
Algidon
Algolysin
Algovetin
Althose hydrochloride
Amidon
Amidone
Biscuits
Butalgin
Depridol
Diaminon
Diaminon hydrochloride
Dollies
Dolly
Dolofin hydrochloride
Dolohepton
Dolophin
Dolophin hydrochloride
Dolophine
Dolophine HCL
Fenadon
Fenadone
Heptadon
Heptadone
Heptanon
Ketalgin
Ketalgin hydrochloride
Mecodin
Mephenon
Methadone HCL Intensol
Methadone M
Methadose
Methaquaione
Miadone
Moheptan
Phenadone
Physeptone
Polamidon
Polamidone
Tussol
Westadone
First Prev Next Last
Brand mixtures Not Available
Categories
  • Narcotics
  • Analgesics
  • Opiate Agonists
  • Antitussives
  • Analgesics, Opioid
  • Antitussive Agents
CAS number 76-99-3
Weight Average: 309.4452
Monoisotopic: 309.209264491
Chemical Formula C21H27NO
InChI Key InChIKey=USSIQXCVUWKGNF-UHFFFAOYSA-N
InChI
InChI=1S/C21H27NO/c1-5-20(23)21(16-17(2)22(3)4,18-12-8-6-9-13-18)19-14-10-7-11-15-19/h6-15,17H,5,16H2,1-4H3
Plain Text
IUPAC Name
6-(dimethylamino)-4,4-diphenylheptan-3-one
SMILES
CCC(=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Diphenylmethanes
Substructures
  • Carbonyl Compounds
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Diphenylmethanes
  • Aromatic compounds
  • Phenylpropylamines
  • Ketones
Pharmacology
Indication For the treatment of dry cough, drug withdrawal syndrome, opioid type drug dependence, and pain.
Pharmacodynamics Methadone is a synthetic opioid analgesic with multiple actions quantitatively similar to those at morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. However, Methadone is more active and more toxic than morphine. Methadone is indicated for relief of severe pain, for detoxification treatment of narcotic addiction, and for temporary maintenance treatment of narcotic addiction. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. The Methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.
Mechanism of action Methadone is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone's efficacy is unknown. Other NMDA receptor antagonists have been shown to produce neurotoxic effects in animals.
Absorption Well absorbed following oral administration. The bioavailability of methadone ranges between 36 to 100%.
Volume of distribution
  • 1.0 to 8.0 L/kg
Protein binding In plasma, methadone is predominantly bound to α1-acid glycoprotein (85% to 90%).
Metabolism Hepatic. Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and CYP2C19 and to a lesser extent CYP2C9 and CYP2D6, are responsible for conversion of methadone to EDDP and other inactive metabolites, which are excreted mainly in the urine.
Route of elimination The elimination of methadone is mediated by extensive biotransformation, followed by renal and fecal excretion. Unmetabolized methadone and its metabolites are excreted in urine to a variable degree.
Half life 24-36 hours
Clearance
  • 1.4 to 126 L/h
Toxicity In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00408 Methadone Pathway SMP00408
Pharmacoeconomics
Manufacturers
  • Roxane laboratories inc
  • Vistapharm inc
  • Mallinckrodt chemical inc
  • Bioniche pharma usa llc
  • Sandoz inc
  • Mallinckrodt inc
  • The pharmanetwork llc
Packagers
Dosage forms
Form Route Strength
Liquid Oral
Solution Oral
Tablet Oral
Prices
Unit description Cost Unit
Methadone hcl 10 mg/ml vial 7.48 USD ml
Methadone hcl powder 5.91 USD g
Metadol 25 mg Tablet 1.69 USD tablet
Metadol 10 mg Tablet 0.9 USD tablet
Methadone intensol 10 mg/ml 0.85 USD ml
Metadol 5 mg Tablet 0.56 USD tablet
Methadone hcl 10 mg tablet 0.37 USD tablet
Metadol Concentrate 10 mg/ml Liquid 0.37 USD ml
Methadone hcl 5 mg tablet 0.34 USD tablet
Dolophine hcl 10 mg tablet 0.21 USD tablet
Metadol 1 mg Tablet 0.17 USD tablet
Methadose 5 mg tablet 0.16 USD tablet
Methadose 10 mg tablet 0.14 USD tablet
Dolophine hcl 5 mg tablet 0.13 USD tablet
Metadol 1 mg/ml Solution 0.1 USD ml
First Prev Next Last
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 235.0 °C Not Available
logP 3.93 HANSCH,C ET AL. (1995)
pKa 8.94 (at 25 °C) PERRIN,DD (1965)
Predicted Properties
Property Value Source
water solubility 5.90e-03 g/l ALOGPS
logP 4.14 ALOGPS
logP 5.01 ChemAxon
logS -4.7 ALOGPS
pKa (strongest acidic) 18.78 ChemAxon
pKa (strongest basic) 9.12 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 20.31 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 97.27 ChemAxon
polarizability 36.29 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Kell MJ: Utilization of plasma and urine methadone concentrations to optimize treatment in maintenance clinics: I. Measurement techniques for a clinical setting. J Addict Dis. 1994;13(1):5-26. Pubmed
  2. Eap CB, Buclin T, Baumann P: Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet. 2002;41(14):1153-93. Pubmed
  3. Joseph H, Stancliff S, Langrod J: Methadone maintenance treatment (MMT): a review of historical and clinical issues. Mt Sinai J Med. 2000 Oct-Nov;67(5-6):347-64. Pubmed
  4. Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, Fry-Smith A, Day E, Lintzeris N, Roberts T, Burls A, Taylor RS: Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation. Health Technol Assess. 2007 Mar;11(9):1-171, iii-iv. Pubmed
  5. Donny EC, Brasser SM, Bigelow GE, Stitzer ML, Walsh SL: Methadone doses of 100 mg or greater are more effective than lower doses at suppressing heroin self-administration in opioid-dependent volunteers. Addiction. 2005 Oct;100(10):1496-509. Pubmed
External Links
Resource Link
KEGG Compound C07163 Link_out
PubChem Compound 4095 Link_out
PubChem Substance 46505722 Link_out
ChemSpider 3953 Link_out
ChEBI 6807 Link_out
ChEMBL 6807 Link_out
Therapeutic Targets Database DAP000267 Link_out
PharmGKB PA450401 Link_out
Drug Product Database 2247698 Link_out
RxList http://www.rxlist.com/cgi/generic/methdone.htm Link_out
Drugs.com http://www.drugs.com/methadone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Methadone Link_out
ATC Codes
  • N02AC52
  • N07BC02
  • R05DA06
AHFS Codes
  • 28:08.08
PDB Entries Not Available
FDA label show (327 KB)
MSDS show (60 KB)
Interactions
Drug Interactions
Drug Interaction
Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Amobarbital The barbiturate, amobarbital, decreases the effect of methadone.
Amprenavir The protease inhibitor, amprenavir, may decrease the effect of methadone.
Aprobarbital The barbiturate, aprobarbital, decreases the effect of methadone.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Butabarbital The barbiturate, butabarbital, decreases the effect of methadone.
Butalbital The barbiturate, butalbital, decreases the effect of methadone.
Butethal The barbiturate, butethal, decreases the effect of methadone.
Carbamazepine Carbamazepine may decrease the serum level of methadone. Monitor for changes in the therapeutic and adverse effects of methadone if carbamazepine is initiated, discontinued or dose changed.
Cimetidine Cimetidine, a moderate CYP3A4 inhibitor, may increase the serum concentration of metahdone, a CYP3A4 substrate. Monitor for changes in the therapeutic and adverse effects of methadone if cimetidine is initiatied, discontinued or dose changed.
Dihydroquinidine barbiturate The barbiturate, dihydroquinidine barbiturate, decreases the effect of methadone.
Efavirenz Efavirenz may decrease the serum concentration of methadone by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of methadone if efavirenz is initiated, discontinued or dose changed.
Eltrombopag Increases levels of Methadone via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
Ethotoin The hydantoin decreases the effect of methadone
Fluvoxamine Fluvoxamine increases the effect and toxicity of methadone
Fosamprenavir The protease inhibitor, fosamprenavir, may decrease the effect of methadone.
Fosphenytoin The hydantoin decreases the effect of methadone
Heptabarbital The barbiturate, heptabarbital, decreases the effect of methadone.
Hexobarbital The barbiturate, hexobarbital, decreases the effect of methadone.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mephenytoin The hydantoin decreases the effect of methadone
Methohexital The barbiturate, methohexital, decreases the effect of methadone.
Methylphenobarbital The barbiturate, methylphenobarbital, decreases the effect of methadone.
Nelfinavir Nelfinavir decreases the effect of methadone
Nevirapine The antiretroviral agent decreases the effect of methadone
Pentobarbital The barbiturate, pentobarbital, decreases the effect of methadone.
Phenobarbital The barbiturate, phenobarbital, decreases the effect of methadone.
Phenytoin The hydantoin decreases the effect of methadone
Primidone The barbiturate, primidone, decreases the effect of methadone.
Quinidine barbiturate The barbiturate, quinidine barbiturate, decreases the effect of methadone.
Rifabutin The rifamycin decreases the effect of methadone
Rifampin The rifamycin decreases the effect of methadone
Rifapentine The rifamycin decreases the effect of methadone
Ritonavir The protease inhibitor, ritonavir, may decrease the effect of methadone.
Secobarbital The barbiturate, secobarbital, decreases the effect of methadone.
St. John's Wort St. John's Wort decreases levels/effect of methadone
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Talbutal The barbiturate, talbutal, decreases the effect of methadone.
Tamoxifen Methadone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin Methadone, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Methadone is initiated, discontinued, or dose changed.
Telithromycin Telithromycin may reduce clearance of Methadone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Methadone if Telithromycin is initiated, discontinued or dose changed.
Thiopental Thiopental may decrease the effect of Methadone by increasing Methadone metabolism. Methadone withdrawal may occur.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Tipranavir Tipranavir, co-administered with Ritonavir, decreases the Methadone concentration. Monitor for symptoms of opiate withdrawal.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Tramadol Methadone may decrease the effect of Tramadol by decreasing active metabolite production.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Triprolidine The CNS depressants, Triprolidine and Methadone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of methadone by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of methadone if voriconazole is initiated, discontinued or dose changed.
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zidovudine Methadone increases the effect and toxicity of zidovudine
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions
  • Take without regard to meals. Avoid alcohol. Usually diluted in fruit juice.
Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out
Gene: OPRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Shi J, Hui L, Xu Y, Wang F, Huang W, Hu G: Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Hum Mutat. 2002 Apr;19(4):459-60. Pubmed
  4. Kakko J, von Wachenfeldt J, Svanborg KD, Lidstrom J, Barr CS, Heilig M: Mood and Neuroendocrine Response to a Chemical Stressor, Metyrapone, in Buprenorphine-Maintained Heroin Dependence. Biol Psychiatry. 2007 Sep 10;. Pubmed
  5. Kvam TM, Baar C, Rakvag TT, Kaasa S, Krokan HE, Skorpen F: Genetic analysis of the murine mu opioid receptor: increased complexity of Oprm gene splicing. J Mol Med. 2004 Apr;82(4):250-5. Epub 2004 Jan 9. Pubmed

2. Glutamate [NMDA] receptor subunit 3A

Pharmacological action: yes
Actions: antagonist

NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism

Organism class: human
UniProt ID: Q8TCU5 Link_out
Gene: GRIN3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Sotgiu ML, Valente M, Storchi R, Caramenti G, Biella GE: Cooperative N-methyl-D-aspartate (NMDA) receptor antagonism and mu-opioid receptor agonism mediate the methadone inhibition of the spinal neuron pain-related hyperactivity in a rat model of neuropathic pain. Pharmacol Res. 2009 Oct;60(4):284-90. Epub 2009 Apr 11. Pubmed

3. Neuronal acetylcholine receptor subunit alpha-10

Pharmacological action: yes
Actions: antagonist

Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma

Organism class: human
UniProt ID: Q9GZZ6 Link_out
Gene: CHRNA10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

4. Delta-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins

Organism class: human
UniProt ID: P41143 Link_out
Gene: OPRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gross ER, Hsu AK, Gross GJ: Acute methadone treatment reduces myocardial infarct size via the delta-opioid receptor in rats during reperfusion. Anesth Analg. 2009 Nov;109(5):1395-402. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. 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. Epub 2009 Nov 24. Pubmed
  4. Kharasch ED, Hoffer C, Whittington D, Sheffels P: Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. Clin Pharmacol Ther. 2004 Sep;76(3):250-69. Pubmed

2. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. 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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A5

Actions: substrate

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 3A7

Actions: substrate

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

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

5. Cytochrome P450 2D6

Actions: substrate, inhibitor

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. 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. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2B6

Actions: substrate

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

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. 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. Epub 2009 Nov 24. Pubmed
  4. Kharasch ED, Hoffer C, Whittington D, Sheffels P: Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. Clin Pharmacol Ther. 2004 Sep;76(3):250-69. Pubmed

7. Cytochrome P450 2C8

Actions: substrate

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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. 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. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 19A1

Actions: substrate

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

UniProt ID: P11511 Link_out
Gene: CYP19A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 1A2

Actions: substrate

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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

10. Cytochrome P450 2C18

Actions: substrate

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

UniProt ID: P33260 Link_out
Gene: CYP2C18 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

11. Cytochrome P450 2C9

Actions: substrate

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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Stormer E, Perloff MD, von Moltke LL, Greenblatt DJ: Methadone inhibits rhodamine123 transport in Caco-2 cells. Drug Metab Dispos. 2001 Jul;29(7):954-6. Pubmed
  2. Tournier N, Chevillard L, Megarbane B, Pirnay S, Scherrmann JM, Decleves X: Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Int J Neuropsychopharmacol. 2010 Aug;13(7):905-15. Epub 2009 Nov 4. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on March 08, 2013 13:35