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Identification
Name Amitriptyline
Accession Number DB00321 (APRD00227)
Type small molecule
Groups approved
Description

Amitriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amitriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, amitriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amitriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Amitriprolidine
Amitriptylin
Amitryptiline
Amitryptyline
Amytriptiline
Salts
  • Amitriptyline Hydrochloride
Brand names
Name Company
Adepress
Adepril
Amitid
Amitril
Damilan
Damilen
Elanil
Elavil
Endep
Flavyl
Horizon
Lantron
Laroxil
Laroxyl
Lentizol
Proheptadiene
Redomex
Saroten
Sarotex
Seroten
Sylvemid
Triptanol
Triptilin
Triptisol
Tryptanol
Tryptizol
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Brand mixtures
Brand Name Ingredients
Apo Peram Tab 2-25 Amitriptyline Hydrochloride + Perphenazine
Apo Peram Tab 3-15 Amitriptyline Hydrochloride + Perphenazine
Elavil Plus Tab Amitriptyline Hydrochloride + Perphenazine
Etrafon 2 10 Amitriptyline Hydrochloride + Perphenazine
Etrafon a Tab Amitriptyline Hydrochloride + Perphenazine
Etrafon D Tab Amitriptyline Hydrochloride + Perphenazine
Etrafon F Tab Amitriptyline Hydrochloride + Perphenazine
Pms-Levazine 2/25 Tab Amitriptyline Hydrochloride + Perphenazine
Pms-Levazine 3/15 Tab Amitriptyline Hydrochloride + Perphenazine
Pms-Levazine 4/25 Tab Amitriptyline Hydrochloride + Perphenazine
Proavil Tab Amitriptyline Hydrochloride + Perphenazine
Triavil Tab Amitriptyline Hydrochloride + Perphenazine
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Categories
  • Adrenergic Uptake Inhibitors
  • Analgesics, Non-Narcotic
  • Antidepressive Agents, Tricyclic
CAS number 50-48-6
Weight Average: 277.4033
Monoisotopic: 277.183049741
Chemical Formula C20H23N
InChI Key InChIKey=KRMDCWKBEZIMAB-UHFFFAOYSA-N
InChI
InChI=1S/C20H23N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3
Plain Text
IUPAC Name
dimethyl({3-[(2Z)-tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene]propyl})amine
SMILES
CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12
Plain Text
Mass Spec show (7.48 KB)
Taxonomy
Kingdom Organic
Classes
  • Dibenzocycloheptenes
Substructures
  • Alkanes and Alkenes
  • Phenylpropenes
  • Benzene and Derivatives
  • Dibenzocycloheptenes
  • Aliphatic and Aryl Amines
  • Isoprenes
  • Aromatic compounds
Pharmacology
Indication For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.
Pharmacodynamics Amitriptyline, a tertiary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is extremely sedating, and thus improvement of sleep patterns can be the first benefit of treatment. Amitriptyline exhibits strong anticholinergic activity, cardiovascular effects including orthostatic hypotension, changes in heart rhythm and conduction, and a lowering of the seizure threshold. As with other antidepressants, several weeks of therapy may be required in order to realize the full clinical benefit of amitriptyline. Although not a labelled indication, amitriptyline is widely used in the management of chronic nonmalignant pain (e.g., post-herpetic neuralgia, fibromyalgia).
Mechanism of action Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
Absorption Rapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations occur 2-12 hours following oral or intramuscular administration.
Volume of distribution Not Available
Protein binding Very highly protein bound (90% or more) in plasma and tissues
Metabolism
Exclusively hepatic, with first pass effect. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Amitriptyline
Nortriptyline Details
Amitriptyline
E-10-Hydroxyamitriptyline Details
E-10-Hydroxyamitriptyline
E-10-Hydroxynortriptyline Details
E-10-Hydroxynortriptyline
    		E-10-Hydroxydesmethylnortriptyline Details
    Nortriptyline
    		E-10-Hydroxynortriptyline Details
    Nortriptyline
      		Desmethylnortriptyline Details
      Desmethylnortriptyline
      		E-10-Hydroxydesmethylnortriptyline Details
      Route of elimination Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours. Small amounts are excreted in feces via biliary elimination.
      Half life 10 to 50 hours, with an average of 15 hours
      Clearance Not Available
      Toxicity LD50=350 mg/kg (in mice). Symptoms of overdose include abnormally low blood pressure, confusion, convulsions, dilated pupils and other eye problems, disturbed concentration, drowsiness, hallucinations, impaired heart function, rapid or irregular heartbeat, reduced body temperature, stupor, and unresponsiveness or coma. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
      Affected organisms
      • Humans and other mammals
      Pathways Not Available
      Pharmacoeconomics
      Manufacturers
      • Hoffmann la roche inc
      • Watson laboratories inc
      • Astrazeneca pharmaceuticals lp
      • Bristol myers squibb co
      • Warner chilcott div warner lambert co
      • American therapeutics inc
      • Caraco pharmaceutical laboratories ltd
      • Copley pharmaceutical inc
      • Halsey drug co inc
      • Lederle laboratories div american cyanamid co
      • Mutual pharmaceutical co inc
      • Mylan pharmaceuticals inc
      • Par pharmaceutical inc
      • Pliva inc
      • Purepac pharmaceutical co
      • Roxane laboratories inc
      • Sandoz inc
      • Superpharm corp
      • Teva pharmaceuticals usa inc
      • Ucb inc
      • Usl pharma inc
      • Vangard laboratories inc div midway medical co
      • Vintage pharmaceuticals inc
      • West ward pharmaceutical corp
      Packagers
      Dosage forms
      Form Route Strength
      Tablet, film coated Oral 10 mg
      Tablet, film coated Oral 100 mg
      Tablet, film coated Oral 150 mg
      Tablet, film coated Oral 25 mg
      Tablet, film coated Oral 50 mg
      Tablet, film coated Oral 75 mg
      Prices
      Unit description Cost Unit
      Amitriptyline hcl powder 7.34 USD g
      Amitriptyline hcl 150 mg tablet 1.18 USD tablet
      Amitriptyline hcl 100 mg tablet 0.66 USD tablet
      Amitriptyline hcl 75 mg tablet 0.54 USD tablet
      Apo-Amitriptyline 75 mg Tablet 0.38 USD tablet
      Amitriptyline hcl 50 mg tablet 0.37 USD tablet
      Amitriptyline hcl 10 mg tablet 0.3 USD tablet
      Apo-Amitriptyline 50 mg Tablet 0.25 USD tablet
      Amitriptyline hcl 25 mg tablet 0.21 USD tablet
      Apo-Amitriptyline 25 mg Tablet 0.13 USD tablet
      Apo-Amitriptyline 10 mg Tablet 0.07 USD tablet
      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 196.5 °C PhysProp
      water solubility 9.71 mg/L (at 24 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
      logP 4.92 HANSCH,C ET AL. (1995)
      logS -4.46 ADME Research, USCD
      pKa 9.4 SANGSTER (1994)
      Predicted Properties
      Property Value Source
      water solubility 4.50e-03 g/l ALOGPS
      logP 5.1 ALOGPS
      logP 4.81 ChemAxon
      logS -4.8 ALOGPS
      pKa (strongest basic) 9.76 ChemAxon
      physiological charge 1 ChemAxon
      hydrogen acceptor count 1 ChemAxon
      hydrogen donor count 0 ChemAxon
      polar surface area 3.24 ChemAxon
      rotatable bond count 3 ChemAxon
      refractivity 101.51 ChemAxon
      polarizability 33.74 ChemAxon
      References
      Synthesis Reference Not Available
      General Reference
      1. Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6. Pubmed
      External Links
      Resource Link
      KEGG Compound C06824 Link_out
      PubChem Compound 2160 Link_out
      PubChem Substance 46508798 Link_out
      ChemSpider 2075 Link_out
      ChEBI 2666 Link_out
      ChEMBL 2666 Link_out
      Therapeutic Targets Database DNC001466 Link_out
      PharmGKB PA448385 Link_out
      IUPHAR 200 Link_out
      Guide to Pharmacology 200 Link_out
      Drug Product Database 654515 Link_out
      RxList http://www.rxlist.com/cgi/generic/amitrip.htm Link_out
      Drugs.com http://www.drugs.com/amitriptyline.html Link_out
      Wikipedia http://en.wikipedia.org/wiki/Amitriptyline Link_out
      ATC Codes
      • N06AA09
      AHFS Codes
      • 28:16.04.28
      PDB Entries Not Available
      FDA label Not Available
      MSDS show (73.6 KB)
      Interactions
      Drug Interactions
      Drug Interaction
      Altretamine Risk of severe hypotension
      Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
      Atazanavir Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if atazanavir if initiated, discontinued or dose changed.
      Butabarbital Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
      Butalbital Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as amitriptyline. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
      Carbamazepine Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if carbamazepine is initiated, discontinued or dose changed.
      Cimetidine Cimetidine may increase the effect of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if cimetidine is initiated, discontinued or dose changed.
      Cisapride Increased risk of cardiotoxicity and arrhythmias
      Clonidine The tricyclic antidepressant, amitriptyline, decreases the effect of clonidine.
      Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
      Dihydroquinidine barbiturate Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, amitriptyline.
      Dobutamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dobutamine.
      Donepezil Possible antagonism of action
      Dopamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dopamine.
      Duloxetine Possible increase in the levels of this agent when used with duloxetine
      Ephedra The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedra.
      Ephedrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedrine.
      Epinephrine The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of epinephrine.
      Fenoterol The tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of fenoterol.
      Fluconazole Fluconazole may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluconazole is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
      Fluoxetine The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluoxetine is initiated, discontinued or dose changed.
      Fluvoxamine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amitriptyline if fluvoxamine is initiated, discontinued or dose changed.
      Galantamine Possible antagonism of action
      Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
      Guanethidine The tricyclic antidepressant, amitriptyline, decreases the effect of guanethidine.
      Indacaterol Concomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
      Iobenguane May diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it inhibits noradrenaline transporter function
      Isocarboxazid Possibility of severe adverse effects
      Isoproterenol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of isoproterenol.
      Ketoconazole Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of amitriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ketoconazole is initiated, discontinued or dose changed.
      Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
      Mephentermine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of mephentermine.
      Mesoridazine Increased risk of cardiotoxicity and arrhythmias
      Metaraminol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of metaraminol.
      Methoxamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of methoxamine.
      Moclobemide Possible severe adverse reaction with this combination
      Norepinephrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of norepinephrine.
      Orciprenaline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of orciprenaline.
      Phenelzine Possibility of severe adverse effects
      Phenylephrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylephrine.
      Phenylpropanolamine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylpropanolamine.
      Pirbuterol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pirbuterol.
      Procaterol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of procaterol.
      Pseudoephedrine The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pseudoephedrine.
      Quinidine Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
      Quinidine barbiturate Quinidine barbiturate increases the effect of tricyclic antidepressant, amitriptyline.
      Rasagiline Possibility of severe adverse effects
      Rifabutin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifabutin is initiated, discontinued or dose changed.
      Rifampin The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if rifampin is initiated, discontinued or dose changed.
      Ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amitriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if ritonavir if initiated, discontinued or dose changed.
      Rivastigmine Possible antagonism of action
      Salbutamol The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of salbutamol.
      Sibutramine Increased risk of CNS adverse effects
      Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
      Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Amitriptyline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
      Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
      Terbinafine Terbinafine may reduce the metabolism and clearance of Amitryptyline. Consider alternate therapy or monitor for therapeutic/adverse effects of Amytriptyline if Terbinafine is initiated, discontinued or dose changed.
      Terbutaline The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of terbutaline.
      Terfenadine Increased risk of cardiotoxicity and arrhythmias
      Thioridazine Increased risk of cardiotoxicity and arrhythmias
      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.
      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 Tramadol increases the risk of serotonin syndrome and seizures.
      Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
      Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
      Trimethobenzamide Trimethobenzamide and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
      Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
      Triprolidine Triprolidine and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
      Trospium Trospium and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
      Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
      Vilazodone Monitor for toxic effects of tricyclic antidepressants if a selective serotonin reuptake inhibitor (SSRI) is initiated or the dose is increased. The influence of the SSRI may take several days or weeks to be fully realized or resolved.
      Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
      Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
      Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
      Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and amitriptyline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
      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
      • Avoid alcohol.
      • Avoid excessive quantities of coffee or tea (caffeine).
      • Avoid St.John's Wort.
      • Take with food to reduce irritation.
      Targets

      1. Sodium-dependent noradrenaline transporter

      Pharmacological action: yes
      Actions: inhibitor

      Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

      Organism class: human
      UniProt ID: P23975 Link_out
      Gene: SLC6A2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. Pubmed
      2. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed

      2. Sodium-dependent serotonin transporter

      Pharmacological action: yes
      Actions: inhibitor

      Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

      Organism class: human
      UniProt ID: P31645 Link_out
      Gene: SLC6A4 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. Pubmed
      2. Troelsen KB, Nielsen EO, Mirza NR: Chronic treatment with duloxetine is necessary for an anxiolytic-like response in the mouse zero maze: the role of the serotonin transporter. Psychopharmacology (Berl). 2005 Oct;181(4):741-50. Epub 2005 Sep 29. Pubmed
      3. Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. Pubmed
      4. Ushijima K, Sakaguchi H, Sato Y, To H, Koyanagi S, Higuchi S, Ohdo S: Chronopharmacological study of antidepressants in forced swimming test of mice. J Pharmacol Exp Ther. 2005 Nov;315(2):764-70. Epub 2005 Aug 3. Pubmed
      5. Kalia M: Neurobiological basis of depression: an update. Metabolism. 2005 May;54(5 Suppl 1):24-7. Pubmed
      6. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed

      3. 5-hydroxytryptamine 2A receptor

      Pharmacological action: yes
      Actions: antagonist

      This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

      Organism class: human
      UniProt ID: P28223 Link_out
      Gene: HTR2A Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

      4. 5-hydroxytryptamine 1A receptor

      Pharmacological action: unknown
      Actions: unknown

      This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

      Organism class: human
      UniProt ID: P08908 Link_out
      Gene: HTR1A Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

      5. Delta-type opioid receptor

      Pharmacological action: unknown
      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. Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. Epub 2009 Oct 14. Pubmed

      6. Kappa-type opioid receptor

      Pharmacological action: unknown
      Actions: agonist

      Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions

      Organism class: human
      UniProt ID: P41145 Link_out
      Gene: OPRK1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Onali P, Dedoni S, Olianas MC: Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):255-65. Epub 2009 Oct 14. Pubmed

      7. High affinity nerve growth factor receptor

      Pharmacological action: unknown
      Actions: agonist

      Required for high-affinity binding to nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 but not brain- derived neurotrophic factor (BDNF). Known substrates for the Trk receptors are SHC1, PI 3-kinase, and PLC-gamma-1. Has a crucial role in the development and function of the nociceptive reception system as well as establishment of thermal regulation via sweating. Activates ERK1 by either SHC1- or PLC-gamma-1-dependent signaling pathway

      Organism class: human
      UniProt ID: P04629 Link_out
      Gene: NTRK1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56. Pubmed

      8. BDNF/NT-3 growth factors receptor

      Pharmacological action: unknown
      Actions: agonist

      Receptor for brain-derived neurotrophic factor (BDNF), neurotrophin-3 and neurotrophin-4/5 but not nerve growth factor (NGF). Involved in the development and/or maintenance of the nervous system. This is a tyrosine-protein kinase receptor. Known substrates for the TRK receptors are SHC1, PI-3 kinase, and PLC- gamma-1

      Organism class: human
      UniProt ID: Q16620 Link_out
      Gene: NTRK2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K: Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009 Jun 26;16(6):644-56. Pubmed

      9. Alpha-1A adrenergic receptor

      Pharmacological action: no
      Actions: antagonist

      This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

      Organism class: human
      UniProt ID: P35348 Link_out
      Gene: ADRA1A Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed
      2. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. Epub 2010 Apr 2. Pubmed

      10. Alpha-1D adrenergic receptor

      Pharmacological action: no
      Actions: antagonist

      This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

      Organism class: human
      UniProt ID: P25100 Link_out
      Gene: ADRA1D Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. Epub 2010 Apr 2. Pubmed

      11. Alpha-2A adrenergic receptor

      Pharmacological action: no
      Actions: antagonist

      Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

      Organism class: human
      UniProt ID: P08913 Link_out
      Gene: ADRA2A Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed
      2. Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6. Pubmed

      12. Histamine H1 receptor

      Pharmacological action: no
      Actions: antagonist

      In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

      Organism class: human
      UniProt ID: P35367 Link_out
      Gene: HRH1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

      13. Muscarinic acetylcholine receptor M1

      Pharmacological action: no
      Actions: antagonist

      The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

      Organism class: human
      UniProt ID: P11229 Link_out
      Gene: CHRM1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

      14. Muscarinic acetylcholine receptor M2

      Pharmacological action: no
      Actions: antagonist

      The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition

      Organism class: human
      UniProt ID: P08172 Link_out
      Gene: CHRM2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

      15. Muscarinic acetylcholine receptor M3

      Pharmacological action: no
      Actions: antagonist

      The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

      Organism class: human
      UniProt ID: P20309 Link_out
      Gene: CHRM3 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

      16. Muscarinic acetylcholine receptor M4

      Pharmacological action: no
      Actions: antagonist

      The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase

      Organism class: human
      UniProt ID: P08173 Link_out
      Gene: CHRM4 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

      17. Muscarinic acetylcholine receptor M5

      Pharmacological action: no
      Actions: antagonist

      The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

      Organism class: human
      UniProt ID: P08912 Link_out
      Gene: CHRM5 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. Pubmed

      18. Potassium voltage-gated channel subfamily KQT member 2

      Pharmacological action: no
      Actions: inhibitor

      Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors

      Organism class: human
      UniProt ID: O43526 Link_out
      Gene: KCNQ2 Link_out
      Protein Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. Pubmed

      19. Potassium voltage-gated channel subfamily A member 1

      Pharmacological action: no
      Actions: inhibitor

      Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient

      Organism class: human
      UniProt ID: Q09470 Link_out
      Gene: KCNA1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. Pubmed

      20. Potassium voltage-gated channel subfamily D member 2

      Pharmacological action: no
      Actions: inhibitor

      Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits

      Organism class: human
      UniProt ID: Q9NZV8 Link_out
      Gene: KCND2 Link_out
      Protein Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. Pubmed

      21. Potassium voltage-gated channel subfamily D member 3

      Pharmacological action: no
      Actions: inhibitor

      Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits

      Organism class: human
      UniProt ID: Q9UK17 Link_out
      Gene: KCND3 Link_out
      Protein Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. Pubmed
      Enzymes

      1. 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. Baumann P: Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69. Pubmed
      2. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. Epub 2008 Feb 14. Pubmed
      3. Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. Pubmed
      4. 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
      5. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      6. 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
      7. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. Pubmed

      2. 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. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. Epub 2008 Feb 14. Pubmed
      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. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      4. Information Hyperlinked Over Proteins (iHOP) – Website
      5. 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. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. Pubmed

      3. Cytochrome P450 2C19

      Actions: substrate, inhibitor

      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. Shin JG, Park JY, Kim MJ, Shon JH, Yoon YR, Cha IJ, Lee SS, Oh SW, Kim SW, Flockhart DA: Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug Metab Dispos. 2002 Oct;30(10):1102-7. Pubmed
      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. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      4. 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
      5. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. Pubmed

      4. 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. Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. Pubmed
      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. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      4. 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
      5. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. Pubmed

      5. Cytochrome P450 3A4

      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 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. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. Epub 2008 Feb 14. Pubmed
      2. Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. Pubmed
      3. 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
      4. 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
      5. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. Pubmed

      6. 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. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. Epub 2008 Feb 14. Pubmed

      7. 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. 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
      2. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. Pubmed

      8. Cytochrome P450 2C8

      Actions: substrate, inhibitor

      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. 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
      2. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37. Pubmed

      9. Cytochrome P450 2E1

      Actions: substrate, inhibitor

      Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

      UniProt ID: P05181 Link_out
      Gene: CYP2E1 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
      Transporters

      1. Multidrug resistance protein 1

      Actions: substrate, 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. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed
      2. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed
      Carriers

      1. Serum albumin

      Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

      UniProt ID: P02768 Link_out
      Gene: ALB Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Brinkschulte M, Breyer-Pfaff U: The contribution of alpha 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):61-6. Pubmed
      2. Banerjee T, Singh SK, Kishore N: Binding of naproxen and amitriptyline to bovine serum albumin: biophysical aspects. J Phys Chem B. 2006 Nov 30;110(47):24147-56. Pubmed

      2. Alpha-1-acid glycoprotein 1

      Appears to function in modulating the activity of the immune system during the acute-phase reaction

      UniProt ID: P02763 Link_out
      Gene: ORM1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Brinkschulte M, Breyer-Pfaff U: The contribution of alpha 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):61-6. Pubmed
      2. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. Pubmed
      Comments
      Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19