DrugBank: Maprotiline (DB00934)

targets (8) enzymes (2) transporters (1) carriers (1)

Identification

Name

Maprotiline

Accession Number

DB00934 (APRD00747)

Type

small molecule

Groups

approved

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Maprotilina [INN-Spanish]
Maprotiline Hcl
Maprotilinum [INN-Latin]
Maprotylina [Polish]

Brand names

Deprilept
Ludiomil
Psymion

Brand name mixtures

Not Available

Categories

Antidepressants
Adrenergic Uptake Inhibitors
Antidepressive Agents, Second-Generation

CAS number

10262-69-8

Weight

Average: 277.4033
Monoisotopic: 277.183049741

Chemical Formula

C₂₀H₂₃N

InChI Key

InChIKey=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

Plain Text

IUPAC Name

methyl(3-{tetracyclo[6.6.2.0^{2,7}.0^{9,14}]hexadeca-2(7),3,5,9(14),10,12-hexaen-1-yl}propyl)amine

SMILES

CNCCCC12CCC(C3=C1C=CC=C3)C1=C2C=CC=C1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Anthracenes

Substructures

Naphthalenes
Aliphatic and Aryl Amines
Benzene and Derivatives
Anthracenes
Aromatic compounds
Cyclohexenes and Derivatives

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.

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.

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.

Enzyme	Metabolite	Reaction	K_m	V_max
Cytochrome P450 2D6	demethylmaprotiline	N-demethylation	71	0

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

Pharmacoeconomics

Manufacturers

Novartis pharmaceuticals corp
American therapeutics inc
Mylan pharmaceuticals inc
Watson laboratories inc

Packagers

Dosage forms

Form	Route	Strength
Tablet	Oral	25 mg
Tablet	Oral	50 mg
Tablet	Oral	75 mg

Prices

Unit description	Cost	Unit
Novo-Maprotiline 75 mg Tablet	1.54 USD	tablet
Maprotiline HCl 75 mg tablet	1.25 USD	tablet
Novo-Maprotiline 50 mg Tablet	1.13 USD	tablet
Maprotiline 75 mg tablet	0.91 USD	tablet
Maprotiline HCl 50 mg tablet	0.86 USD	tablet
Maprotiline 50 mg tablet	0.79 USD	tablet
Maprotiline HCl 25 mg tablet	0.73 USD	tablet
Maprotiline 25 mg tablet	0.69 USD	tablet
Novo-Maprotiline 25 mg Tablet	0.6 USD	tablet

Patents

Not Available

Properties

State

solid

Melting point

93 oC

Experimental Properties

Property	Value	Source
water solubility	Slightly soluble	PhysProp
logP	5.1	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.50e-04 g/l	ALOGPS
logP	4.89	ALOGPS
logP	4.37	ChemAxon Molconvert
logS	-6.27	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	1	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	12.03	ChemAxon Molconvert
rotatable bond count	4	ChemAxon Molconvert
refractivity	99.30	ChemAxon Molconvert
polarizability	33.57	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D02566
KEGG Compound	C07107
PubChem Compound	4011
PubChem Substance	46508358
ChemSpider	3871
BindingDB	35228
Therapeutic Targets Database	DAP001150
PharmGKB	PA450322
Drug Product Database	0
Drugs.com	http://www.drugs.com/cdi/maprotiline.html
Wikipedia	http://en.wikipedia.org/wiki/Maprotiline

ATC Codes

N06AA21

AHFS Codes

28:16.04.28

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (64.8 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Take without regard to meals. Limit caffeine intake.

Targets
1. Sodium-dependent noradrenaline transporter Pharmacological action: yes Actions: inhibitor Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals Organism class: human UniProt ID: P23975 Gene: SLC6A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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. Pubmed 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 Mochizucki D: Serotonin and noradrenaline reuptake inhibitors in animal models of pain. Hum Psychopharmacol. 2004 Oct;19 Suppl 1:S15-9. Pubmed 2. Histamine H1 receptor Pharmacological action: no Actions: antagonist In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system Organism class: human UniProt ID: P35367 Gene: HRH1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. Pubmed 3. Muscarinic acetylcholine receptor M1 Pharmacological action: no Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: human UniProt ID: P11229 Gene: CHRM1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 4. Muscarinic acetylcholine receptor M2 Pharmacological action: no Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition Organism class: human UniProt ID: P08172 Gene: CHRM2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 5. Muscarinic acetylcholine receptor M3 Pharmacological action: no Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: human UniProt ID: P20309 Gene: CHRM3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 6. Muscarinic acetylcholine receptor M4 Pharmacological action: no Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase Organism class: human UniProt ID: P08173 Gene: CHRM4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 7. Muscarinic acetylcholine receptor M5 Pharmacological action: no Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: human UniProt ID: P08912 Gene: CHRM5 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 8. Alpha-1A adrenergic receptor Pharmacological action: no Actions: antagonist This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins Organism class: human UniProt ID: P35348 Gene: ADRA1A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Targets

1. Sodium-dependent noradrenaline transporter

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P23975 Link_out

Gene: SLC6A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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. Pubmed
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
Mochizucki D: Serotonin and noradrenaline reuptake inhibitors in animal models of pain. Hum Psychopharmacol. 2004 Oct;19 Suppl 1:S15-9. Pubmed

2. Histamine H1 receptor

Pharmacological action: no
Actions: antagonist

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

Organism class: human
UniProt ID: P35367 Link_out

Gene: HRH1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. Pubmed

3. Muscarinic acetylcholine receptor M1

Pharmacological action: no
Actions: antagonist

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

Organism class: human
UniProt ID: P11229 Link_out

Gene: CHRM1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

4. Muscarinic acetylcholine receptor M2

Pharmacological action: no
Actions: antagonist

Organism class: human
UniProt ID: P08172 Link_out

Gene: CHRM2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

5. Muscarinic acetylcholine receptor M3

Pharmacological action: no
Actions: antagonist

Organism class: human
UniProt ID: P20309 Link_out

Gene: CHRM3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

6. Muscarinic acetylcholine receptor M4

Pharmacological action: no
Actions: antagonist

Organism class: human
UniProt ID: P08173 Link_out

Gene: CHRM4 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

7. Muscarinic acetylcholine receptor M5

Pharmacological action: no
Actions: antagonist

Organism class: human
UniProt ID: P08912 Link_out

Gene: CHRM5 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

8. Alpha-1A adrenergic receptor

Pharmacological action: no
Actions: antagonist

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

Organism class: human
UniProt ID: P35348 Link_out

Gene: ADRA1A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Enzymes
1. Cytochrome P450 2D6 Actions: substrate Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants UniProt ID: P10635 Gene: CYP2D6 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 2. Cytochrome P450 1A2 Actions: substrate Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177 Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out

Gene: CYP2D6 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

2. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out

Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters
1. Multidrug resistance protein 1 Actions: inhibitor Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183 Gene: ABCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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

Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out

Gene: ABCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

Carriers
1. Alpha-1-acid glycoprotein 1 Appears to function in modulating the activity of the immune system during the acute-phase reaction UniProt ID: P02763 Gene: ORM1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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

Carriers

1. Alpha-1-acid glycoprotein 1

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

UniProt ID: P02763 Link_out

Gene: ORM1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

Comments

Drug created on June 13, 2005 07:24 / Updated on October 19, 2011 13:14

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.