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Identification
NameNortriptyline
Accession NumberDB00540  (APRD00602)
TypeSmall Molecule
GroupsApproved
Description

Nortriptyline hydrochloride, the N-demethylated active metabolite of amitriptyline, 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, nortriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, nortriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline. 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. Nortriptyline exerts less anticholinergic and sedative side effects compared to the tertiary amine TCAs, amitriptyline and clomipramine. Nortriptyline 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
10,11-dihydro-N-Methyl-5H-dibenzo[a,D]cycloheptene-delta(5,gamma)-propylamineNot AvailableNot Available
3-(10,11-dihydro-5H-Dibenzo[a,D]cyclohepten-5-ylidene)-N-methyl-1-propanamineNot AvailableNot Available
AtebenNot AvailableNot Available
AvantylNot AvailableNot Available
AventylNot AvailableNot Available
DemethylamitriptylineNot AvailableNot Available
DesmethylamitriptylineNot AvailableNot Available
NoritrenNot AvailableNot Available
NortriptylineNot AvailableNot Available
PsychostylNot AvailableNot Available
SensavalNot AvailableNot Available
Salts
Name/CAS Structure Properties
Nortriptyline Hydrochloride
Thumb
  • InChI Key: SHAYBENGXDALFF-UHFFFAOYSA-N
  • Monoisotopic Mass: 299.144077416
  • Average Mass: 299.838
DBSALT000641
Brand names
NameCompany
AllegronNot Available
AventylNot Available
NoritrenNot Available
NorpressNot Available
NortrilenNot Available
PamelorNot Available
SensovalNot Available
Brand mixturesNot Available
Categories
CAS number72-69-5
WeightAverage: 263.3767
Monoisotopic: 263.167399677
Chemical FormulaC19H21N
InChI KeyPHVGLTMQBUFIQQ-UHFFFAOYSA-N
InChI
InChI=1S/C19H21N/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19/h2-5,7-11,20H,6,12-14H2,1H3
IUPAC Name
methyl({3-[(2E)-tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene]propyl})amine
SMILES
CNCCC=C1C2=CC=CC=C2CCC2=CC=CC=C12
Mass Specshow(7.76 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassDibenzocycloheptenes
SubclassNot Available
Direct parentDibenzocycloheptenes
Alternative parentsBenzene and Substituted Derivatives; Dialkylamines; Polyamines
Substituentsbenzene; secondary aliphatic amine; polyamine; secondary amine; 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.
PharmacodynamicsSimilar to protriptyline, nortriptyline is a tricyclic antidepressant of the dibenzocycloheptene type and is the active metabolite of amitriptyline.
Mechanism of actionIt is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at beta-adrenergic receptors. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake.
AbsorptionWell absorbed from the GI tract. Peak plasma concentrations occur 7-8.5 hours following oral administration.
Volume of distributionNot Available
Protein bindingHighly protein-bound in plasma and tissues.
Metabolism

Undergoes hepatic metabolism via the same pathway as other TCAs.

SubstrateEnzymesProduct
Nortriptyline
E-10-HydroxynortriptylineDetails
Nortriptyline
DesmethylnortriptylineDetails
E-10-Hydroxynortriptyline
Not Available
E-10-HydroxydesmethylnortriptylineDetails
Desmethylnortriptyline
E-10-HydroxydesmethylnortriptylineDetails
Route of eliminationApproximately one-third of a single orally administered dose is excreted in urine within 24 hours. Small amounts are excreted in feces via biliary elimination.
Half life16 to 90+ hours
ClearanceNot Available
ToxicitySymptoms of overdose include cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. 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
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
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9478
Caco-2 permeable + 0.774
P-glycoprotein substrate Substrate 0.7863
P-glycoprotein inhibitor I Inhibitor 0.8876
P-glycoprotein inhibitor II Inhibitor 0.5376
Renal organic cation transporter Inhibitor 0.6903
CYP450 2C9 substrate Non-substrate 0.7508
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.5593
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.7665
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5194
Ames test Non AMES toxic 0.5315
Carcinogenicity Non-carcinogens 0.9182
Biodegradation Ready biodegradable 0.5
Rat acute toxicity 2.7513 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.5809
hERG inhibition (predictor II) Inhibitor 0.7763
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Taro pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Tyco healthcare group lp
  • Ranbaxy pharmaceuticals inc
  • Pharmaceutical assoc inc
  • Taro pharmaceutical industries ltd
Packagers
Dosage forms
FormRouteStrength
CapsuleOral10 mg
CapsuleOral25 mg
CapsuleOral50 mg
CapsuleOral75 mg
SolutionOral10 mg/5 ml
Prices
Unit descriptionCostUnit
Pamelor 30 10 mg capsule Bottle750.05USDbottle
Pamelor 30 25 mg capsule Bottle750.05USDbottle
Pamelor 30 50 mg capsule Bottle750.05USDbottle
Pamelor 10 mg/5ml Solution 480ml Bottle325.97USDbottle
Pamelor 10 mg capsule24.04USDcapsule
Pamelor 25 mg capsule24.04USDcapsule
Pamelor 50 mg capsule24.04USDcapsule
Pamelor 75 mg capsule19.34USDcapsule
Nortriptyline hcl powder11.09USDg
Nortriptyline hcl 75 mg capsule1.33USDcapsule
Nortriptyline hcl 50 mg capsule0.94USDcapsule
Nortriptyline hcl 25 mg capsule0.6USDcapsule
Aventyl 25 mg Capsule0.48USDcapsule
Nortriptyline HCl 10 mg/5ml Solution0.4USDml
Nortriptyline hcl 10 mg capsule0.28USDcapsule
Apo-Nortriptyline 25 mg Capsule0.27USDcapsule
Novo-Nortriptyline 25 mg Capsule0.27USDcapsule
Nu-Nortriptyline 25 mg Capsule0.27USDcapsule
Pms-Nortriptyline 25 mg Capsule0.27USDcapsule
Aventyl 10 mg Capsule0.24USDcapsule
Apo-Nortriptyline 10 mg Capsule0.13USDcapsule
Novo-Nortriptyline 10 mg Capsule0.13USDcapsule
Nu-Nortriptyline 10 mg Capsule0.13USDcapsule
Pms-Nortriptyline 10 mg Capsule0.13USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point213-215 °CNot Available
logP4.51BRODIN,A (1974)
pKa10.1SANGSTER (2004)
Predicted Properties
PropertyValueSource
Water Solubility0.000874ALOGPS
logP4.65ALOGPS
logP4.43ChemAxon
logS-5.5ALOGPS
pKa (Strongest Basic)10.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity96.21 m3·mol-1ChemAxon
Polarizability31.87 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
References
Synthesis Reference

Abraham Nudelman, “ACID ADDITION SALT OF A NORTRIPTYLINE-GABA CONJUGATE AND A PROCESS OF PREPARING SAME.” U.S. Patent US20130184347, issued July 18, 2013.

US20130184347
General Reference
  1. Prochazka AV, Weaver MJ, Keller RT, Fryer GE, Licari PA, Lofaso D: A randomized trial of nortriptyline for smoking cessation. Arch Intern Med. 1998 Oct 12;158(18):2035-9. Pubmed
External Links
ResourceLink
KEGG CompoundC07274
PubChem Compound4543
PubChem Substance46507783
ChemSpider4384
ChEBI7640
ChEMBLCHEMBL445
Therapeutic Targets DatabaseDAP001152
PharmGKBPA450657
IUPHAR2404
Guide to Pharmacology2404
Drug Product Database2240789
RxListhttp://www.rxlist.com/cgi/generic/nortrip.htm
Drugs.comhttp://www.drugs.com/nortriptyline.html
WikipediaNortriptyline
ATC CodesN06AA10
AHFS Codes
  • 28:16.04.28
PDB EntriesNot Available
FDA labelshow(420 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AltretamineRisk of hypotension
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
AtazanavirAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if atazanavir if initiated, discontinued or dose changed.
ButabarbitalBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like nortriptyline. 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 nortriptyline. 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, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if carbamazepine is initiated, discontinued or dose changed.
CimetidineCimetidine may increase the effect of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if cimetidine is initiated, discontinued or dose changed.
CisaprideIncreased risk of cardiotoxicity and arrhythmias
ClonidineThe tricyclic antidepressant, nortriptyline, 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, nortriptyline.
DobutamineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of dobutamine.
DonepezilPossible antagonism of action
DopamineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of dopamine.
DuloxetinePossible increase in the levels of this agent when used with duloxetine
EphedraThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of ephedra.
EphedrineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of ephedrine.
EpinephrineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of epinephrine.
FenoterolThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of fenoterol.
FluconazoleFluconazole may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of nortriptyline 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, nortriptyline, 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 nortriptyline if fluoxetine is initiated, discontinued or dose changed.
FluvoxamineThe SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, nortriptyline, 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 nortriptyline if fluvoxamine is initiated, discontinued or dose changed.
GalantaminePossible antagonism of action
GrepafloxacinIncreased risk of cardiotoxicity and arrhythmias
GuanethidineThe tricyclic antidepressant, nortriptyline, decreases the effect of guanethidine.
IsocarboxazidPossibility of severe adverse effects
IsoprenalineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of isoproterenol.
KetoconazoleKetoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of nortriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ketoconazole is initiated, discontinued or dose changed.
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MephentermineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of mephentermine.
MetaraminolThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of metaraminol.
MethoxamineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of methoxamine.
MoclobemidePossible severe adverse reaction with this combination
NorepinephrineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of norepinephrine.
OrciprenalineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of orciprenaline.
PhenelzinePossibility of severe adverse effects
PhenylephrineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of phenylephrine.
PhenylpropanolamineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of phenylpropanolamine.
PirbuterolThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of pirbuterol.
ProcaterolThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of procaterol.
PseudoephedrineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of pseudoephedrine.
QuinidineAdditive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline 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 the tricyclic antidepressant, nortriptyline.
RasagilinePossibility of severe adverse effects
RifabutinThe rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifabutin is initiated, discontinued or dose changed.
RifampicinThe rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifampin is initiated, discontinued or dose changed.
RitonavirRitonavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ritonavir if initiated, discontinued or dose changed.
RivastigminePossible antagonism of action
SalbutamolThe tricyclic antidepressant, nortriptyline, 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, Nortriptyline, 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 increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if terbinafine is initiated, discontinued or dose changed.
TerbutalineThe tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of terbutaline.
TerfenadineIncreased 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 Nortriptyline, 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 Nortriptyline, 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 Nortriptyline, 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 nortriptyline, 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).
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (caffeine).
  • Take with food to reduce irritation.

Targets

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. Roubert C, Cox PJ, Bruss M, Hamon M, Bonisch H, Giros B: Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity. J Biol Chem. 2001 Mar 16;276(11):8254-60. Epub 2000 Nov 22. Pubmed
  2. Roubert C, Sagne C, Kapsimali M, Vernier P, Bourrat F, Giros B: A Na(+)/Cl(-)-dependent transporter for catecholamines, identified as a norepinephrine transporter, is expressed in the brain of the teleost fish medaka (Oryzias latipes). Mol Pharmacol. 2001 Sep;60(3):462-73. 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. Kim H, Lim SW, Kim S, Kim JW, Chang YH, Carroll BJ, Kim DK: Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression. JAMA. 2006 Oct 4;296(13):1609-18. Pubmed
  5. Barker EL, Blakely RD: Identification of a single amino acid, phenylalanine 586, that is responsible for high affinity interactions of tricyclic antidepressants with the human serotonin transporter. Mol Pharmacol. 1996 Oct;50(4):957-65. 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

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. Joyce PR, Mulder RT, Luty SE, McKenzie JM, Miller AL, Rogers GR, Kennedy MA: Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline. Int J Neuropsychopharmacol. 2003 Dec;6(4):339-46. Pubmed
  2. Wisner KL, Hanusa BH, Perel JM, Peindl KS, Piontek CM, Sit DK, Findling RL, Moses-Kolko EL: Postpartum depression: a randomized trial of sertraline versus nortriptyline. J Clin Psychopharmacol. 2006 Aug;26(4):353-60. Pubmed
  3. Pollock BG, Ferrell RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, Davis S, Kirshner MA, Houck PR, Stack JA, Reynolds CF, Kupfer DJ: Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology. 2000 Nov;23(5):587-90. Pubmed
  4. 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
  5. Rausch JL, Moeller FG, Johnson ME: Initial platelet serotonin (5-HT) transport kinetics predict nortriptyline treatment outcome. J Clin Psychopharmacol. 2003 Apr;23(2):138-44. 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: antagonist

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. 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
  2. Sadava D, Wilmington K: Tricyclic antidepressant drugs affect histamine receptors in human leukocytes. Life Sci. 1984 Dec 17;35(25):2545-8. Pubmed

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 5-hydroxytryptamine receptor 2C

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

References:

  1. Palvimaki EP, Roth BL, Majasuo H, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J: Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology (Berl). 1996 Aug;126(3):234-40. Pubmed

14. 5-hydroxytryptamine receptor 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 6 P50406 Details

References:

  1. National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Oct 3]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
  2. Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.
  3. Monsma FJ Jr, Shen Y, Ward RP, Hamblin MW, Sibley DR: Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol. 1993 Mar;43(3):320-7. Pubmed

15. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 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. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. Pubmed

16. Alpha-2 adrenergic receptor

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details
Alpha-2B adrenergic receptor P18089 Details
Alpha-2C adrenergic receptor P18825 Details

References:

  1. National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Oct 3]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
  2. Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.

17. Beta adrenergic receptor

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Beta-1 adrenergic receptor P08588 Details
Beta-2 adrenergic receptor P07550 Details
Beta-3 adrenergic receptor P13945 Details

References:

  1. National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Oct 3]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
  2. Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.

18. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

  1. Peroutka SJ, Snyder SH: Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet. 1982 Mar 20;1(8273):658-9. Pubmed
  2. National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Oct 3]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
  3. Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.

19. Sigma receptor

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Membrane-associated progesterone receptor component 1 O00264 Details
Sigma non-opioid intracellular receptor 1 Q99720 Details

References:

  1. National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Oct 3]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
  2. Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.

20. 5-hydroxytryptamine receptor 1C

Kind: protein

Organism: Rat

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P08909 Details

References:

  1. Jenck F, Moreau JL, Mutel V, Martin JR, Haefely WE: Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur J Pharmacol. 1993 Feb 9;231(2):223-9. Pubmed

Enzymes

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. 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. 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: Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): implications for interactions with enzyme-inducing drugs. J Clin Pharmacol. 1999 Jun;39(6):567-77. Pubmed
  6. Olesen OV, Linnet K: Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. Drug Metab Dispos. 1997 Jun;25(6):740-4. Pubmed

2. 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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): implications for interactions with enzyme-inducing drugs. J Clin Pharmacol. 1999 Jun;39(6):567-77. Pubmed

3. 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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. Olesen OV, Linnet K: Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. Drug Metab Dispos. 1997 Jun;25(6):740-4. Pubmed

4. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Olesen OV, Linnet K: Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. Drug Metab Dispos. 1997 Jun;25(6):740-4. Pubmed

5. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

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

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. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

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

8. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: 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

Carriers

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. 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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11