Identification

Name
Maprotiline
Accession Number
DB00934  (APRD00747)
Type
Small Molecule
Groups
Approved, Investigational
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
  • Maprotiline
  • Maprotilinum
  • Maprotylina
Product Ingredients
IngredientUNIICASInChI Key
Maprotiline Hydrochloride7C8J54PVFI10347-81-6NZDMFGKECODQRY-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LudiomilTablet75 mg/1OralNovartis1980-12-012008-10-30Us
LudiomilTablet25 mg/1OralNovartis1980-12-012008-10-30Us
LudiomilTablet50 mg/1OralNovartis1980-12-012008-10-30Us
Ludiomil Tab 10mgTablet10 mgOralNovartis1985-12-312003-07-29Canada
Ludiomil Tab 25mgTablet25 mgOralNovartis1976-12-312001-07-30Canada
Ludiomil Tab 50mgTablet50 mgOralNovartis1976-12-312001-07-30Canada
Ludiomil Tab 75mgTablet75 mgOralNovartis1976-12-312000-08-02Canada
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
Novo-maprotiline - Tab 10mgTablet10 mgOralNovopharm Limited1995-12-312005-08-10Canada
PMS-maprotilineTablet25 mgOralPharmascience IncNot applicableNot applicableCanada
PMS-maprotilineTablet75 mgOralPharmascience IncNot applicableNot applicableCanada
PMS-maprotilineTablet10 mgOralPharmascience IncNot applicableNot applicableCanada
PMS-maprotilineTablet50 mgOralPharmascience IncNot applicableNot applicableCanada
Teva-maprotilineTablet50 mgOralTeva1995-12-31Not applicableCanada
Teva-maprotilineTablet25 mgOralTeva1995-12-31Not applicableCanada
International/Other Brands
Deprilept / Ludiomil / Psymion
Categories
UNII
2U1W68TROF
CAS number
10262-69-8
Weight
Average: 277.4033
Monoisotopic: 277.183049741
Chemical Formula
C20H23N
InChI Key
QSLMDECMDJKHMQ-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

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Maprotiline 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 action

Maprotiline 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.

TargetActionsOrganism
ASodium-dependent noradrenaline transporter
inhibitor
Human
NHistamine H1 receptor
antagonist
Human
NMuscarinic acetylcholine receptor M1
antagonist
Human
NMuscarinic acetylcholine receptor M2
antagonist
Human
NMuscarinic acetylcholine receptor M3
antagonist
Human
NMuscarinic acetylcholine receptor M4
antagonist
Human
NMuscarinic acetylcholine receptor M5
antagonist
Human
NAlpha-1 adrenergic receptors
antagonist
Human
U5-hydroxytryptamine receptor 2A
binder
Human
U5-hydroxytryptamine receptor 2C
binder
Human
U5-hydroxytryptamine receptor 7
antagonist
Human
UD(2) dopamine receptor
binder
Human
UAlpha-2 adrenergic receptors
antagonist
Human
Absorption

Slowly, 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 binding

88%

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.

Route of elimination

Approximately 60% of a single orally administered dose is excreted in urine as conjugated metabolites within 21 days; 30% is eliminated in feces.

Half life

Average ~ 51 hours (range: 27-58 hours)

Clearance
Not Available
Toxicity

LD50=~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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Maprotiline.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Maprotiline is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of Maprotiline can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Maprotiline is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Maprotiline is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Maprotiline.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Maprotiline is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Maprotiline is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Maprotiline is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Maprotiline is combined with 4-Methoxyamphetamine.
Food Interactions
  • Take without regard to meals. Limit caffeine intake.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015069
KEGG Drug
D02566
KEGG Compound
C07107
PubChem Compound
4011
PubChem Substance
46508358
ChemSpider
3871
BindingDB
35228
ChEBI
6690
ChEMBL
CHEMBL21731
Therapeutic Targets Database
DAP001150
PharmGKB
PA450322
IUPHAR
2402
Guide to Pharmacology
GtP Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Maprotiline
ATC Codes
N06AA21 — Maprotiline
AHFS Codes
  • 28:16.04.28 — Tricyclics and Other Norepinephrine-reuptake Inhibitors
MSDS
Download (64.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
  • American therapeutics inc
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
Packagers
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novartis AG
  • Prescript Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral25 mg/1
TabletOral50 mg/1
TabletOral75 mg/1
TabletOral25 mg
TabletOral50 mg
TabletOral75 mg
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral75 mg/1
TabletOral10 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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)93 °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 RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0f6x-9560000000-f263c228ecd4df5d7e73
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0090000000-7a66545f7844123eba51
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0fb9-0090000000-c3b045151955339e59cc
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0gb9-0590000000-bfeab480527e9e5cb70a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0930000000-406a233a8ad8a3b5d463
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-002f-0920000000-d86cbfa85ef229dfed53
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0090000000-1a2bf3822fc21e2f8460
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0fb9-0190000000-cf4d09e63ae607c3f690
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gb9-1690000000-32657b0912154e5e6eb5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-1940000000-176ec01fb7ad9b4a11ca
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-1920000000-a721293bed4aff937490
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-1910000000-f2d680cb6b1ab57df4bd
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0390000000-ae291d01fb28cc38d1de

Taxonomy

Description
This compound belongs to the class of organic compounds known as anthracenes. These are organic compounds containing a system of three linearly fused benzene rings.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Anthracenes
Sub Class
Not Available
Direct Parent
Anthracenes
Alternative Parents
Tetralins / Aralkylamines / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Anthracene / Tetralin / Aralkylamine / Secondary amine / Secondary aliphatic amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Amine
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
anthracenes (CHEBI:6690)

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
Uniprot Name
Sodium-dependent noradrenaline transporter
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]
Details
2. Histamine H1 receptor
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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
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...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
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...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
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...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
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...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
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...
Gene Name
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
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) prot...

Components:
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-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
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-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
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 ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
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
Uniprot Name
D(2) dopamine receptor
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 oxymetazo...

Components:
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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]
  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]
  3. Maprotiline Data Sheet [File]

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...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
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]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 17:08