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Identification
NameAmitriptyline
Accession NumberDB00321  (APRD00227)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
AmitriptilinaNot AvailableDCIT
AmitriptylinGermanINN
AmitriptylineNot AvailableDCF, BAN
AmitriptylinumLatinINN
Salts
Name/CAS Structure Properties
Amitriptyline Hydrochloride
Thumb
  • InChI Key: KFYRPLNVJVHZGT-UHFFFAOYSA-N
  • Monoisotopic Mass: 313.15972748
  • Average Mass: 313.864
DBSALT000009
Brand names
NameCompany
AdeprilTeofarma
AmitrypRaza
ConmitripCondrugs
ElavilGerda
EndepAlphapharm
FiordaDriburg
KamitrinSaga
LaroxylDeva
LatilinLa Pharmaceuticals
MaxitripInvision
RedomexLundbeck
SarotenLundbeck
SarotexLundbeck
Sarotex RetardLundbeck
SyneudonKrewel Meuselbach
TryptanolMerck Sharp & Dohme
TryptanolSquare
TryptizolAlgorithm
Uxen RetardSanofi-Aventis
Brand mixtures
Brand NameIngredients
Elavil PlusAmitriptyline Hydrochloride + Perphenazine
EtrafonAmitriptyline Hydrochloride + Perphenazine
PMS-LevazineAmitriptyline Hydrochloride + Perphenazine
ProavilAmitriptyline Hydrochloride + Perphenazine
TriavilAmitriptyline Hydrochloride + Perphenazine
Categories
CAS number50-48-6
WeightAverage: 277.4033
Monoisotopic: 277.183049741
Chemical FormulaC20H23N
InChI KeyInChIKey=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
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
Mass Specshow(7.48 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassDibenzocycloheptenes
SubclassNot Available
Direct parentDibenzocycloheptenes
Alternative parentsBenzene and Substituted Derivatives; Tertiary Amines; Polyamines
Substituentsbenzene; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the dibenzocycloheptenes. These are compounds containing a dibenzocycloheptene moiety, which consists of two benzene connected by a cycloheptene ring.
Pharmacology
IndicationFor the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.
PharmacodynamicsAmitriptyline, 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 actionAmitriptyline 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.
AbsorptionRapidly 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 distributionNot Available
Protein bindingVery 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.

SubstrateEnzymesProduct
Amitriptyline
NortriptylineDetails
Amitriptyline
E-10-HydroxyamitriptylineDetails
E-10-Hydroxyamitriptyline
E-10-HydroxynortriptylineDetails
E-10-Hydroxynortriptyline
    E-10-HydroxydesmethylnortriptylineDetails
    Nortriptyline
    E-10-HydroxynortriptylineDetails
    Nortriptyline
      DesmethylnortriptylineDetails
      Desmethylnortriptyline
      E-10-HydroxydesmethylnortriptylineDetails
      Route of eliminationVirtually 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 life10 to 50 hours, with an average of 15 hours
      ClearanceNot Available
      ToxicityLD50=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
      PathwaysNot Available
      SNP Mediated Effects
      Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
      Cytochrome P450 2D6
      Gene symbol: CYP2D6
      UniProt: P10635
      rs3892097 CYP2D6*4A AllelePoor drug metabolizer, lower dose requirements, higher risk for adverse side effects18070221
      Multidrug resistance protein 1
      Gene symbol: ABCB1
      UniProt: P08183
      rs2032583 Not AvailableC AlleleImproved response to antidepressant medication17913323
      Multidrug resistance protein 1
      Gene symbol: ABCB1
      UniProt: P08183
      rs2032583 Not AvailableA > GIncrease risk of adverse effects22641028
      SNP Mediated Adverse Drug Reactions
      Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
      Multidrug resistance protein 1
      Gene symbol: ABCB1
      UniProt: P08183
      rs1045642 Not AvailableT Allele, homozygousPostural hypotension12082591
      Cytochrome P450 2C19
      Gene symbol: CYP2C19
      UniProt: P33261
      rs4244285 CYP2C19*2G > AThose with the AA or AG genotype are poor metabolizers of amitriptyline20531370
      Cytochrome P450 2D6
      Gene symbol: CYP2D6
      UniProt: P10635
      rs3892097 CYP2D6*4C > TIncrease risk of side effects and decrease drug metabolism18070221
      Cytochrome P450 2D6
      Gene symbol: CYP2D6
      UniProt: P10635
      rs3892097 CYP2D6*4C > TIncrease risk of side effects and decrease drug metabolism9918137
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption + 0.9941
      Blood Brain Barrier + 0.9512
      Caco-2 permeable + 0.8867
      P-glycoprotein substrate Substrate 0.7567
      P-glycoprotein inhibitor I Inhibitor 0.8563
      P-glycoprotein inhibitor II Inhibitor 0.6447
      Renal organic cation transporter Inhibitor 0.7955
      CYP450 2C9 substrate Non-substrate 0.7826
      CYP450 2D6 substrate Substrate 0.8918
      CYP450 3A4 substrate Substrate 0.7501
      CYP450 1A2 substrate Inhibitor 0.7324
      CYP450 2C9 substrate Non-inhibitor 0.9071
      CYP450 2D6 substrate Inhibitor 0.8933
      CYP450 2C19 substrate Non-inhibitor 0.9025
      CYP450 3A4 substrate Non-inhibitor 0.9158
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6955
      Ames test Non AMES toxic 0.9132
      Carcinogenicity Non-carcinogens 0.8127
      Biodegradation Not ready biodegradable 0.8727
      Rat acute toxicity 2.9697 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.7531
      hERG inhibition (predictor II) Inhibitor 0.6767
      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
      FormRouteStrength
      Tablet, film coatedOral10 mg
      Tablet, film coatedOral100 mg
      Tablet, film coatedOral150 mg
      Tablet, film coatedOral25 mg
      Tablet, film coatedOral50 mg
      Tablet, film coatedOral75 mg
      Prices
      Unit descriptionCostUnit
      Amitriptyline hcl powder7.34USDg
      Amitriptyline hcl 150 mg tablet1.18USDtablet
      Amitriptyline hcl 100 mg tablet0.66USDtablet
      Amitriptyline hcl 75 mg tablet0.54USDtablet
      Apo-Amitriptyline 75 mg Tablet0.38USDtablet
      Amitriptyline hcl 50 mg tablet0.37USDtablet
      Amitriptyline hcl 10 mg tablet0.3USDtablet
      Apo-Amitriptyline 50 mg Tablet0.25USDtablet
      Amitriptyline hcl 25 mg tablet0.21USDtablet
      Apo-Amitriptyline 25 mg Tablet0.13USDtablet
      Apo-Amitriptyline 10 mg Tablet0.07USDtablet
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      PatentsNot Available
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point187-189.5Tristram, E.W. and Tull, R.J.; US. Patent 3,205,264: September 7,1965; assigned to Merck & Co., Inc.
      water solubility9.71 mg/L (at 24 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
      logP4.92HANSCH,C ET AL. (1995)
      logS-4.46ADME Research, USCD
      pKa9.4SANGSTER (1994)
      Predicted Properties
      PropertyValueSource
      water solubility4.50e-03 g/lALOGPS
      logP5.1ALOGPS
      logP4.81ChemAxon
      logS-4.8ALOGPS
      pKa (strongest basic)9.76ChemAxon
      physiological charge1ChemAxon
      hydrogen acceptor count1ChemAxon
      hydrogen donor count0ChemAxon
      polar surface area3.24ChemAxon
      rotatable bond count3ChemAxon
      refractivity101.51ChemAxon
      polarizability33.74ChemAxon
      number of rings3ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleYesChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis Reference

      Manfred Durr, Benedikt Gajdos, Klaus-Dieter Gneuss, Ekkehard Harhausen, Jurgen Seidel, “Pharmaceutical amitriptylin oxide preparation and process for its manufacture.” U.S. Patent US4567202, issued January 28, 1986.

      US4567202
      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
      ResourceLink
      KEGG CompoundC06824
      PubChem Compound2160
      PubChem Substance46508798
      ChemSpider2075
      ChEBI2666
      ChEMBLCHEMBL629
      Therapeutic Targets DatabaseDNC001466
      PharmGKBPA448385
      IUPHAR200
      Guide to Pharmacology200
      Drug Product Database654515
      RxListhttp://www.rxlist.com/cgi/generic/amitrip.htm
      Drugs.comhttp://www.drugs.com/amitriptyline.html
      WikipediaAmitriptyline
      ATC CodesN06AA09
      AHFS Codes
      • 28:16.04.28
      PDB EntriesNot Available
      FDA labelNot Available
      MSDSshow(73.6 KB)
      Interactions
      Drug Interactions
      Drug
      AltretamineRisk of severe hypotension
      ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
      AtazanavirAtazanavir 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.
      ButabarbitalBarbiturates 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.
      ButalbitalBarbiturates 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.
      CarbamazepineCarbamazepine 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.
      CimetidineCimetidine 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.
      CisaprideIncreased risk of cardiotoxicity and arrhythmias
      ClonidineThe tricyclic antidepressant, amitriptyline, decreases the effect of clonidine.
      DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
      Dihydroquinidine barbiturateDihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, amitriptyline.
      DobutamineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dobutamine.
      DonepezilPossible antagonism of action
      DopamineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect, dopamine.
      DuloxetinePossible increase in the levels of this agent when used with duloxetine
      EphedraThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedra.
      EphedrineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of ephedrine.
      EpinephrineThe tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of epinephrine.
      FenoterolThe tricyclic antidepressant, amitriptyline, may increase the sympathomimetic effect of fenoterol.
      FluconazoleFluconazole 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.
      FluoxetineThe 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.
      FluvoxamineThe 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.
      GalantaminePossible antagonism of action
      GrepafloxacinIncreased risk of cardiotoxicity and arrhythmias
      GuanethidineThe tricyclic antidepressant, amitriptyline, decreases the effect of guanethidine.
      IndacaterolConcomitant 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.
      IobenguaneMay diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it inhibits noradrenaline transporter function
      IsocarboxazidPossibility of severe adverse effects
      IsoprenalineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of isoproterenol.
      KetoconazoleKetoconazole, 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.
      LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
      MephentermineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of mephentermine.
      MesoridazineIncreased risk of cardiotoxicity and arrhythmias
      MetaraminolThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of metaraminol.
      MethoxamineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of methoxamine.
      MoclobemidePossible severe adverse reaction with this combination
      NorepinephrineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of norepinephrine.
      OrciprenalineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of orciprenaline.
      PhenelzinePossibility of severe adverse effects
      PhenylephrineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylephrine.
      PhenylpropanolamineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of phenylpropanolamine.
      PirbuterolThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pirbuterol.
      ProcaterolThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of procaterol.
      PseudoephedrineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of pseudoephedrine.
      QuinidineAdditive 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 barbiturateQuinidine barbiturate increases the effect of tricyclic antidepressant, amitriptyline.
      RasagilinePossibility of severe adverse effects
      RifabutinThe 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.
      RifampicinThe 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.
      RitonavirRitonavir 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.
      RivastigminePossible antagonism of action
      SalbutamolThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of salbutamol.
      SibutramineIncreased risk of CNS adverse effects
      SparfloxacinIncreased risk of cardiotoxicity and arrhythmias
      TacrineThe 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.
      TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
      TerbinafineTerbinafine 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.
      TerbutalineThe tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of terbutaline.
      TerfenadineIncreased risk of cardiotoxicity and arrhythmias
      ThioridazineIncreased risk of cardiotoxicity and arrhythmias
      ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
      ToremifeneAdditive 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.
      TramadolTramadol increases the risk of serotonin syndrome and seizures.
      TranylcypromineIncreased 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.
      TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
      TrimethobenzamideTrimethobenzamide and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
      TrimipramineIncreased 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.
      TriprolidineTriprolidine 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.
      TrospiumTrospium and Amitriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
      VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
      VilazodoneMonitor 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.
      VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
      VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
      ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
      ZolmitriptanUse 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.
      ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
      Zuclopenthixol acetateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
      Zuclopenthixol decanoateAdditive 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.

      1. Sodium-dependent noradrenaline transporter

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Sodium-dependent noradrenaline transporter P23975 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Sodium-dependent serotonin transporter P31645 Details

      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 receptor 2A

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: antagonist

      Components

      Name UniProt ID Details
      5-hydroxytryptamine receptor 2A P28223 Details

      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 receptor 1A

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: unknown

      Components

      Name UniProt ID Details
      5-hydroxytryptamine receptor 1A P08908 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: agonist

      Components

      Name UniProt ID Details
      Delta-type opioid receptor P41143 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: agonist

      Components

      Name UniProt ID Details
      Kappa-type opioid receptor P41145 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: agonist

      Components

      Name UniProt ID Details
      High affinity nerve growth factor receptor P04629 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: agonist

      Components

      Name UniProt ID Details
      BDNF/NT-3 growth factors receptor Q16620 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Alpha-1A adrenergic receptor P35348 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Alpha-1D adrenergic receptor P25100 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Alpha-2A adrenergic receptor P08913 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Histamine H1 receptor P35367 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Muscarinic acetylcholine receptor M1 P11229 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Muscarinic acetylcholine receptor M2 P08172 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Muscarinic acetylcholine receptor M3 P20309 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Muscarinic acetylcholine receptor M4 P08173 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: antagonist

      Components

      Name UniProt ID Details
      Muscarinic acetylcholine receptor M5 P08912 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Potassium voltage-gated channel subfamily KQT member 2 O43526 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Potassium voltage-gated channel subfamily A member 1 Q09470 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Potassium voltage-gated channel subfamily D member 2 Q9NZV8 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Potassium voltage-gated channel subfamily D member 3 Q9UK17 Details

      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

      1. Cytochrome P450 2D6

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 2D6 P10635 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 1A2 P05177 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 2C19 P33261 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 2C9 P11712 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 3A4 P08684 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 3A5 P20815 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 2B6 P20813 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 2C8 P10632 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 2E1 P05181 Details

      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

      1. Serum albumin

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Components

      Name UniProt ID Details
      Serum albumin P02768 Details

      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

      Kind: protein

      Organism: Human

      Pharmacological action: no

      Components

      Name UniProt ID Details
      Alpha-1-acid glycoprotein 1 P02763 Details

      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

      1. Multidrug resistance protein 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Multidrug resistance protein 1 P08183 Details

      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

      Comments
      Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09