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Identification
NameMaprotiline
Accession NumberDB00934  (APRD00747)
TypeSmall Molecule
GroupsApproved
Description

Maprotiline is a tetracyclic antidepressant with similar pharmacological properties to tricyclic antidepressants (TCAs). Similar to TCAs, maprotiline inhibits neuronal norepinephrine reuptake, possesses some anticholinergic activity, and does not affect monoamine oxidase activity. It differs from TCAs in that it does not appear to block serotonin reuptake. Maprotiline may be used to treat depressive affective disorders, including dysthymic disorder (depressive neurosis) and major depressive disorder. Maprotiline is effective at reducing symptoms of anxiety associated with depression.

Structure
Thumb
Synonyms
Maprotilina
Maprotilinum
Maprotylina
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ludiomil Tab 10mgtablet10 mgoralNovartis Pharmaceuticals Canada Inc1985-12-312003-07-29Canada
Ludiomil Tab 25mgtablet25 mgoralNovartis Pharmaceuticals Canada Inc1976-12-312001-07-30Canada
Ludiomil Tab 50mgtablet50 mgoralNovartis Pharmaceuticals Canada Inc1976-12-312001-07-30Canada
Ludiomil Tab 75mgtablet75 mgoralNovartis Pharmaceuticals Canada Inc1976-12-312000-08-02Canada
Novo-maprotiline - Tab 10mgtablet10 mgoralNovopharm Limited1995-12-312005-08-10Canada
PMS-maprotilinetablet10 mgoralPharmascience IncNot applicableNot applicableCanada
PMS-maprotilinetablet75 mgoralPharmascience IncNot applicableNot applicableCanada
PMS-maprotilinetablet50 mgoralPharmascience IncNot applicableNot applicableCanada
PMS-maprotilinetablet25 mgoralPharmascience IncNot applicableNot applicableCanada
Teva-maprotilinetablet75 mgoralTeva Canada Limited1995-12-31Not applicableCanada
Teva-maprotilinetablet25 mgoralTeva Canada Limited1995-12-31Not applicableCanada
Teva-maprotilinetablet50 mgoralTeva Canada Limited1995-12-31Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Maprotiline Hydrochloridetablet, film coated25 mg/1oralMylan Pharmaceuticals Inc.1988-10-03Not applicableUs
Maprotiline Hydrochloridetablet, film coated75 mg/1oralMylan Pharmaceuticals Inc.1988-10-03Not applicableUs
Maprotiline Hydrochloridetablet, film coated50 mg/1oralMylan Pharmaceuticals Inc.1988-10-03Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DeprileptNot Available
LudiomilNot Available
PsymionNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Maprotiline Hydrochloride
Thumb
  • InChI Key: NZDMFGKECODQRY-UHFFFAOYSA-N
  • Monoisotopic Mass: 313.15972748
  • Average Mass: 313.864
DBSALT000482
Categories
UNII2U1W68TROF
CAS number10262-69-8
WeightAverage: 277.4033
Monoisotopic: 277.183049741
Chemical FormulaC20H23N
InChI KeyQSLMDECMDJKHMQ-UHFFFAOYSA-N
InChI
InChI=1S/C20H23N/c1-21-14-6-12-20-13-11-15(16-7-2-4-9-18(16)20)17-8-3-5-10-19(17)20/h2-5,7-10,15,21H,6,11-14H2,1H3
IUPAC Name
methyl(3-{tetracyclo[6.6.2.0²,⁷.0⁹,¹⁴]hexadeca-2,4,6,9,11,13-hexaen-1-yl}propyl)amine
SMILES
CNCCCC12CCC(C3=CC=CC=C13)C1=CC=CC=C21
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as anthracenes. These are organic compounds containing a system of three linearly fused benzene rings.
KingdomOrganic compounds
Super ClassBenzenoids
ClassAnthracenes
Sub ClassNot Available
Direct ParentAnthracenes
Alternative Parents
Substituents
  • Anthracene
  • Tetralin
  • Aralkylamine
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor treatment of depression, including the depressed phase of bipolar depression, psychotic depression, and involutional melancholia, and may also be helpful in treating certain patients suffering severe depressive neurosis.
PharmacodynamicsMaprotiline is a tetracyclic antidepressant. Although its main therapeutic use is in the treatment of depression, it has also been shown to exert a sedative effect on the anxiety component that often accompanies depression. In one sleep study, it was shown that maprotiline increases the duration of the REM sleep phase in depressed patients, compared to imipramine which reduced the REM sleep phase. Maprotiline is a strong inhibitor of noradrenaline reuptake in the brain and peripheral tissues, however it is worthy to note that it is a weak inhibitor of serotonergic uptake. In addition, it displays strong antihistaminic action (which may explain its sedative effects) as well as weak anticholinergic action. Maprotiline also has lower alpha adrenergic blocking activity than amitriptyline.
Mechanism of actionMaprotiline exerts its antidepressant action by inhibition of presynaptic uptake of catecholamines, thereby increasing their concentration at the synaptic clefts of the brain. In single doses, the effect of maprotiline on the EEG revealed a rise in the alpha-wave density, a reduction of the alpha-wave frequency and an increase in the alpha-wave amplitude. However, as with other tricyclic antidepressants, maprotiline lowers the convulsive threshold. Maprotiline acts as an antagonist at central presynaptic α2-adrenergic inhibitory autoreceptors and hetero-receptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity. Maprotiline is also a moderate peripheral α1 adrenergic antagonist, which may explain the occasional orthostatic hypotension reported in association with its use. Maprotiline also inhibits the amine transporter, delaying the reuptake of noradrenaline and norepinephrine. Lastly, maprotiline is a strong inhibitor of the histamine H1 receptor, which explains its sedative actions.
Related Articles
AbsorptionSlowly, but completely absorbed from the GI tract following oral administration.
Volume of distribution

Maprotiline and its metabolites may be detected in the lungs, liver, brain, and kidneys; lower concentrations may be found in the adrenal glands, heart and muscle. Maprotiline is readily distributed into breast milk to similar concentrations as those in maternal blood.

Protein binding88%
Metabolism

Hepatic. Maprotiline is metabolized by N-demethylation, deamination, aliphatic and aromatic hydroxylations and by formation of aromatic methoxy derivatives. It is slowly metabolized primarily to desmethylmaprotiline, a pharmacologically active metabolite. Desmethylmaprotiline may undergo further metabolism to maprotiline-N-oxide.

SubstrateEnzymesProduct
Maprotiline
demethylmaprotilineDetails
Route of eliminationApproximately 60% of a single orally administered dose is excreted in urine as conjugated metabolites within 21 days; 30% is eliminated in feces.
Half lifeAverage ~ 51 hours (range: 27-58 hours)
ClearanceNot Available
ToxicityLD50=~900 mg/kg (Orally in rats); LD50=90 mg/kg (Orally in women); Signs of overdose include motor unrest, muscular twitching and rigidity, tremor, ataxia, convulsions, hyperpyrexia, vertigo, mydriasis, vomiting, cyanosis, hypotension, shock, tachycardia, cardiac arrhythmias, impaired cardiac conduction, respiratory depression, and disturbances of consciousness up to deep coma.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9903
Caco-2 permeable+0.7214
P-glycoprotein substrateSubstrate0.7836
P-glycoprotein inhibitor IInhibitor0.7667
P-glycoprotein inhibitor IIInhibitor0.7206
Renal organic cation transporterInhibitor0.6502
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.5216
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.855
Ames testNon AMES toxic0.7713
CarcinogenicityNon-carcinogens0.9204
BiodegradationNot ready biodegradable0.8913
Rat acute toxicity2.5307 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7016
hERG inhibition (predictor II)Inhibitor0.8652
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • American therapeutics inc
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedoral25 mg/1
Tablet, film coatedoral50 mg/1
Tablet, film coatedoral75 mg/1
Tabletoral10 mg
Tabletoral25 mg
Tabletoral50 mg
Tabletoral75 mg
Prices
Unit descriptionCostUnit
Novo-Maprotiline 75 mg Tablet1.54USD tablet
Maprotiline HCl 75 mg tablet1.25USD tablet
Novo-Maprotiline 50 mg Tablet1.13USD tablet
Maprotiline 75 mg tablet0.91USD tablet
Maprotiline HCl 50 mg tablet0.86USD tablet
Maprotiline 50 mg tablet0.79USD tablet
Maprotiline HCl 25 mg tablet0.73USD tablet
Maprotiline 25 mg tablet0.69USD tablet
Novo-Maprotiline 25 mg Tablet0.6USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point93 °CPhysProp
water solubilitySlightly solubleNot Available
logP5.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00015 mg/mLALOGPS
logP4.89ALOGPS
logP4.37ChemAxon
logS-6.3ALOGPS
pKa (Strongest Basic)10.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity99.3 m3·mol-1ChemAxon
Polarizability33.57 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-0f6x-9560000000-f263c228ecd4df5d7e73View in MoNA
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesN06AA21
AHFS Codes
  • 28:16.04.28
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (64.8 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Maprotiline can be increased when it is combined with Abiraterone.
AcepromazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Acepromazine.
AcetophenazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Acetophenazine.
AclidiniumAclidinium may increase the anticholinergic activities of Maprotiline.
AmisulprideThe risk or severity of adverse effects can be increased when Maprotiline is combined with Amisulpride.
AripiprazoleThe risk or severity of adverse effects can be increased when Maprotiline is combined with Aripiprazole.
AzelastineMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Maprotiline.
BenzquinamideThe risk or severity of adverse effects can be increased when Maprotiline is combined with Benzquinamide.
Botulinum Toxin Type AMaprotiline may increase the anticholinergic activities of Botulinum Toxin Type A.
Botulinum Toxin Type BMaprotiline may increase the anticholinergic activities of Botulinum Toxin Type B.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
BuprenorphineMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
CarphenazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Carphenazine.
ChlormezanoneThe risk or severity of adverse effects can be increased when Maprotiline is combined with Chlormezanone.
ChlorpromazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Chlorpromazine.
ChlorpropamideMaprotiline may increase the hypoglycemic activities of Chlorpropamide.
ChlorprothixeneThe risk or severity of adverse effects can be increased when Maprotiline is combined with Chlorprothixene.
Cimetropium BromideMaprotiline may increase the anticholinergic activities of Cimetropium Bromide.
CitalopramMaprotiline may increase the QTc-prolonging activities of Citalopram.
ClozapineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Clozapine.
CobicistatThe serum concentration of Maprotiline can be increased when it is combined with Cobicistat.
DapoxetineThe risk or severity of adverse effects can be increased when Dapoxetine is combined with Maprotiline.
DarunavirThe serum concentration of Maprotiline can be increased when it is combined with Darunavir.
DofetilideMaprotiline may increase the QTc-prolonging activities of Dofetilide.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
EluxadolineMaprotiline may increase the activities of Eluxadoline.
EthanolMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
FencamfamineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Fencamfamine.
FluoxetineThe metabolism of Maprotiline can be decreased when combined with Fluoxetine.
FlupentixolThe risk or severity of adverse effects can be increased when Maprotiline is combined with Flupentixol.
FluphenazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Fluphenazine.
FluspirileneThe risk or severity of adverse effects can be increased when Maprotiline is combined with Fluspirilene.
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Maprotiline.
Glucagon recombinantThe risk or severity of adverse effects can be increased when Maprotiline is combined with Glucagon recombinant.
GoserelinMaprotiline may increase the QTc-prolonging activities of Goserelin.
GranisetronGranisetron may increase the serotonergic activities of Maprotiline.
HaloperidolThe risk or severity of adverse effects can be increased when Maprotiline is combined with Haloperidol.
HydrocodoneMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
Ipratropium bromideIpratropium bromide may increase the anticholinergic activities of Maprotiline.
IsocarboxazidThe risk or severity of adverse effects can be increased when Maprotiline is combined with Isocarboxazid.
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Maprotiline.
LeuprolideMaprotiline may increase the QTc-prolonging activities of Leuprolide.
LinezolidThe risk or severity of adverse effects can be increased when Maprotiline is combined with Linezolid.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Maprotiline.
LoxapineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Loxapine.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
MesoridazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Mesoridazine.
MethotrimeprazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Methotrimeprazine.
Methylene blueMaprotiline may increase the serotonergic activities of Methylene blue.
MetoclopramideThe risk or severity of adverse effects can be increased when Maprotiline is combined with Metoclopramide.
MetyrosineMaprotiline may increase the sedative activities of Metyrosine.
MianserinMianserin may increase the anticholinergic activities of Maprotiline.
MifepristoneMifepristone may increase the QTc-prolonging activities of Maprotiline.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
MirabegronThe risk or severity of adverse effects can be increased when Maprotiline is combined with Mirabegron.
MoclobemideThe risk or severity of adverse effects can be increased when Maprotiline is combined with Moclobemide.
MolindoneThe risk or severity of adverse effects can be increased when Maprotiline is combined with Molindone.
MorphineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Morphine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
OlanzapineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Olanzapine.
OndansetronThe risk or severity of adverse effects can be increased when Maprotiline is combined with Ondansetron.
OrphenadrineMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
PaliperidoneThe risk or severity of adverse effects can be increased when Maprotiline is combined with Paliperidone.
PanobinostatThe serum concentration of Maprotiline can be increased when it is combined with Panobinostat.
ParaldehydeMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
Peginterferon alfa-2bThe serum concentration of Maprotiline can be decreased when it is combined with Peginterferon alfa-2b.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
PerphenazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Perphenazine.
PhenelzineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Phenelzine.
PimozideThe risk or severity of adverse effects can be increased when Maprotiline is combined with Pimozide.
PiperacetazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Piperacetazine.
Potassium ChlorideMaprotiline may increase the ulcerogenic activities of Potassium Chloride.
PramipexoleMaprotiline may increase the sedative activities of Pramipexole.
PramlintidePramlintide may increase the anticholinergic activities of Maprotiline.
ProcarbazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Procarbazine.
ProchlorperazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Prochlorperazine.
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Maprotiline.
PromazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Promazine.
QuetiapineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Quetiapine.
RamosetronMaprotiline may increase the activities of Ramosetron.
RasagilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Rasagiline.
RemoxiprideThe risk or severity of adverse effects can be increased when Maprotiline is combined with Remoxipride.
ReserpineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Reserpine.
RisperidoneThe risk or severity of adverse effects can be increased when Maprotiline is combined with Risperidone.
RitonavirThe metabolism of Maprotiline can be decreased when combined with Ritonavir.
RopiniroleMaprotiline may increase the sedative activities of Ropinirole.
RotigotineMaprotiline may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Maprotiline.
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Maprotiline.
SelegilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Selegiline.
SertindoleThe risk or severity of adverse effects can be increased when Maprotiline is combined with Sertindole.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Maprotiline.
SuvorexantMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TacrineThe therapeutic efficacy of Maprotiline can be decreased when used in combination with Tacrine.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Maprotiline.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Maprotiline is combined with Tedizolid Phosphate.
ThalidomideMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
ThioridazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Thioridazine.
ThiothixeneThe risk or severity of adverse effects can be increased when Maprotiline is combined with Thiothixene.
TiclopidineThe metabolism of Maprotiline can be decreased when combined with Ticlopidine.
TiotropiumMaprotiline may increase the anticholinergic activities of Tiotropium.
TopiramateThe risk or severity of adverse effects can be increased when Maprotiline is combined with Topiramate.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Maprotiline.
TranylcypromineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Tranylcypromine.
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Maprotiline.
TrifluoperazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Trifluoperazine.
TriflupromazineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Triflupromazine.
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Maprotiline.
ZiprasidoneThe risk or severity of adverse effects can be increased when Maprotiline is combined with Ziprasidone.
ZolpidemMaprotiline may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
ZuclopenthixolThe risk or severity of adverse effects can be increased when Maprotiline is combined with Zuclopenthixol.
Food Interactions
  • Take without regard to meals. Limit caffeine intake.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular Weight:
69331.42 Da
References
  1. Saba W, Valette H, Schollhorn-Peyronneau MA, Coulon C, Ottaviani M, Chalon S, Dolle F, Emond P, Halldin C, Helfenbein J, Madelmont JC, Deloye JB, Guilloteau D, Bottlaender M: [11C]LBT-999: a suitable radioligand for investigation of extra-striatal dopamine transporter with PET. Synapse. 2007 Jan;61(1):17-23. [PubMed:17068778 ]
  2. Arai S, Morita K, Kitayama S, Kumagai K, Kumagai M, Kihira K, Dohi T: Chronic inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics. Brain Res. 2003 Feb 21;964(1):83-90. [PubMed:12573515 ]
  3. Cloonan SM, Drozgowska A, Fayne D, Williams DC: The antidepressants maprotiline and fluoxetine have potent selective antiproliferative effects against Burkitt lymphoma independently of the norepinephrine and serotonin transporters. Leuk Lymphoma. 2010 Mar;51(3):523-39. doi: 10.3109/10428190903552112. [PubMed:20141432 ]
  4. Dronjak S, Spasojevic N, Gavrilovic L, Varagic V: Effects of noradrenaline and serotonin reuptake inhibitors on pituitary-adrenocortical and sympatho-adrenomedullar system of adult rats. Neuro Endocrinol Lett. 2007 Oct;28(5):614-20. [PubMed:17984940 ]
  5. Mochizucki D: Serotonin and noradrenaline reuptake inhibitors in animal models of pain. Hum Psychopharmacol. 2004 Oct;19 Suppl 1:S15-9. [PubMed:15378668 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
References
  1. Noguchi S, Inukai T, Kuno T, Tanaka C: The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking. Physiol Behav. 1992 Jun;51(6):1123-7. [PubMed:1353628 ]
  2. Cavero I, Lefevre-Borg F, Roach AG: Effects of mianserin, desipramine and maprotiline on blood pressure responses evoked by acetylcholine, histamine and 5-hydroxytryptamine in rats. Br J Pharmacol. 1981 Sep;74(1):143-8. [PubMed:6115693 ]
  3. Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. [PubMed:6146381 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
References
  1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [PubMed:6297650 ]
  2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [PubMed:7052344 ]
  3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [PubMed:6118411 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then trigge...
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
References
  1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [PubMed:6297650 ]
  2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [PubMed:7052344 ]
  3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [PubMed:6118411 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
References
  1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [PubMed:6297650 ]
  2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [PubMed:7052344 ]
  3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [PubMed:6118411 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da
References
  1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [PubMed:6297650 ]
  2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [PubMed:7052344 ]
  3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [PubMed:6118411 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM5
Uniprot ID:
P08912
Molecular Weight:
60073.205 Da
References
  1. El-Fakahany E, Richelson E: Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol. 1983 Jan;78(1):97-102. [PubMed:6297650 ]
  2. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [PubMed:7052344 ]
  3. Doggrell SA, Vincent L: The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle. J Pharm Pharmacol. 1981 Nov;33(11):720-4. [PubMed:6118411 ]
Kind
Protein group
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Components:
NameUniProt IDDetails
Alpha-1A adrenergic receptorP35348 Details
Alpha-1B adrenergic receptorP35368 Details
Alpha-1D adrenergic receptorP25100 Details
References
  1. Buckley NA, McManus PR: Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug Saf. 1998 May;18(5):369-81. [PubMed:9589848 ]
  2. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates...
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
References
  1. Peroutka SJ, Lebovitz RM, Snyder SH: Two distinct central serotonin receptors with different physiological functions. Science. 1981 May 15;212(4496):827-9. [PubMed:7221567 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modul...
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
References
  1. Peroutka SJ, Lebovitz RM, Snyder SH: Two distinct central serotonin receptors with different physiological functions. Science. 1981 May 15;212(4496):827-9. [PubMed:7221567 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:
HTR7
Uniprot ID:
P34969
Molecular Weight:
53554.43 Da
References
  1. Lucchelli A, Santagostino-Barbone MG, D'Agostino G, Masoero E, Tonini M: The interaction of antidepressant drugs with enteric 5-HT7 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):284-9. [PubMed:10997731 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da
References
  1. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881 ]
Kind
Protein group
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Components:
NameUniProt IDDetails
Alpha-2A adrenergic receptorP08913 Details
Alpha-2B adrenergic receptorP18089 Details
Alpha-2C adrenergic receptorP18825 Details
References
  1. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Brachtendorf L, Jetter A, Beckurts KT, Holscher AH, Fuhr U: Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol. 2002 Mar;90(3):144-9. [PubMed:12071336 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
no
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
References
  1. 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:2870173 ]
  2. Eap CB, Cuendet C, Baumann P: Selectivity in the binding of psychotropic drugs to the variants of alpha-1 acid glycoprotein. Naunyn Schmiedebergs Arch Pharmacol. 1988 Feb;337(2):220-4. [PubMed:3368020 ]
  3. Lynn K, Braithwaite R, Dawling S, Rosser R: Comparison of the serum protein binding of maprotiline and phenytoin in uraemic patients on haemodialysis. Eur J Clin Pharmacol. 1981 Jan;19(1):73-7. [PubMed:7461027 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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:12438524 ]
  2. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103 ]
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Drug created on June 13, 2005 07:24 / Updated on October 16, 2015 13:21