DrugBank: Methotrimeprazine (DB01403)

targets (19) enzymes (3)

Identification

Name

Methotrimeprazine

Accession Number

DB01403

Type

small molecule

Groups

approved

Description

A phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)

Structure

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

Synonyms

Levomepromazine

Brand names

Levoprome
Neozine
Neurocil
Nosinan
Nozinan

Brand name mixtures

Not Available

Categories

Dopamine Antagonists
Analgesics, Non-Narcotic
Antipsychotic Agents

CAS number

60-99-1

Weight

Average: 328.472
Monoisotopic: 328.160934090

Chemical Formula

C₁₉H₂₄N₂OS

InChI Key

InChIKey=VRQVVMDWGGWHTJ-CQSZACIVSA-N

InChI

InChI=1S/C19H24N2OS/c1-14(12-20(2)3)13-21-16-7-5-6-8-18(16)23-19-10-9-15(22-4)11-17(19)21/h5-11,14H,12-13H2,1-4H3/t14-/m1/s1

Plain Text

IUPAC Name

[(2R)-3-(2-methoxy-10H-phenothiazin-10-yl)-2-methylpropyl]dimethylamine

SMILES

COC1=CC=C2SC3=C(C=CC=C3)N(C[C@H](C)CN(C)C)C2=C1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Phenothiazines

Substructures

Ethers
Phenothiazines
Phenols and Derivatives
Aliphatic and Aryl Amines
Thiazines
Benzene and Derivatives
Heterocyclic compounds
Aromatic compounds
Anisoles
Phenyl Esters
Anilines

Pharmacology

Indication

For the treatment of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder.

Pharmacodynamics

Methotrimeprazine is a phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)

Mechanism of action

Methotrimeprazine's antipsychotic effect is largely due to its antagonism of dopamine receptors in the brain. In addition, its binding to 5HT2 receptors may also play a role.

Absorption

Methotrimeprazine has an incomplete oral bioavailability, because it undergoes considerable first-pass-metabolism in the liver. Oral bioavailability is approximately 50 to 60%.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic. Methotrimeprazine is metabolized in the liver and degraded to a sulfoxid-, a glucuronid- and a demethyl-moiety.

Route of elimination

Not Available

Half life

Approximately 20 hours.

Clearance

Not Available

Toxicity

Symptoms of overdose include convulsions, spastic movements, and coma.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Immunex corp

Packagers

Not Available

Dosage forms

Form	Route	Strength
Solution	Intramuscular
Tablet	Oral

Prices

Unit description	Cost	Unit
Nozinan 25 mg/ml	3.6 USD	ml
Apo-Methoprazine 50 mg Tablet	0.4 USD	tablet
Apo-Methoprazine 25 mg Tablet	0.27 USD	tablet
Apo-Methoprazine 5 mg Tablet	0.1 USD	tablet
Apo-Methoprazine 2 mg Tablet	0.07 USD	tablet

Patents

Not Available

Properties

State

solid

Melting point

Not Available

Experimental Properties

Property	Value	Source
logP	4.68 [HANSCH,C ET AL. (1995)]	PhysProp
logS	-4.22 [ADME Research, USCD]	PhysProp
pKa	9.19	Various sources

Predicted Properties

Property	Value	Source
water solubility	5.25e-03 g/l	ALOGPS
logP	4.84	ALOGPS
logP	4.25	ChemAxon Molconvert
logS	-4.80	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	3	ChemAxon Molconvert
hydrogen donor count	0	ChemAxon Molconvert
polar surface area	15.71	ChemAxon Molconvert
rotatable bond count	5	ChemAxon Molconvert
refractivity	99.83	ChemAxon Molconvert
polarizability	36.77	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Link

External Links

Resource	Link
KEGG Drug	D00403
KEGG Compound	C07192
PubChem Compound	72287
PubChem Substance	46507223
ChemSpider	65239
ChEBI	6838
ChEMBL	6838
PharmGKB	PA13468794
Drug Product Database	1927655
Wikipedia	http://en.wikipedia.org/wiki/Levomepromazine

ATC Codes

N05AA02

AHFS Codes

28:16.08.24

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Take with food to reduce irritation.

Targets
1. D(2) dopamine receptor Pharmacological action: yes Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase Organism class: human UniProt ID: P14416 Gene: DRD2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed 2. D(1A) dopamine receptor Pharmacological action: unknown Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase Organism class: human UniProt ID: P21728 Gene: DRD1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed 3. D(1B) dopamine receptor Pharmacological action: unknown Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase Organism class: human UniProt ID: P21918 Gene: DRD5 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed 4. D(3) dopamine receptor Pharmacological action: unknown Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase Organism class: human UniProt ID: P35462 Gene: DRD3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed 5. D(4) dopamine receptor Pharmacological action: unknown Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase Organism class: human UniProt ID: P21917 Gene: DRD4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed 6. 5-hydroxytryptamine 2A receptor Pharmacological action: unknown Actions: antagonist 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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production Organism class: human UniProt ID: P28223 Gene: HTR2A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed 7. 5-hydroxytryptamine 2C receptor Pharmacological action: unknown Actions: antagonist 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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system Organism class: human UniProt ID: P28335 Gene: HTR2C Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed 8. Histamine H1 receptor Pharmacological action: unknown 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: Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed 9. Muscarinic acetylcholine receptor M1 Pharmacological action: unknown 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: Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed 10. Muscarinic acetylcholine receptor M2 Pharmacological action: unknown 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: Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed 11. Muscarinic acetylcholine receptor M3 Pharmacological action: unknown 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: Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed 12. Muscarinic acetylcholine receptor M4 Pharmacological action: unknown 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: Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed 13. Muscarinic acetylcholine receptor M5 Pharmacological action: unknown 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: Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed 14. Alpha-1A adrenergic receptor Pharmacological action: unknown 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: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed 15. Alpha-1B adrenergic receptor Pharmacological action: unknown Actions: antagonist This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system Organism class: human UniProt ID: P35368 Gene: ADRA1B Protein Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed 16. Alpha-1D adrenergic receptor Pharmacological action: unknown Actions: antagonist This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium Organism class: human UniProt ID: P25100 Gene: ADRA1D Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed 17. Alpha-2A adrenergic receptor Pharmacological action: unknown Actions: antagonist 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 Organism class: human UniProt ID: P08913 Gene: ADRA2A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Tsukamoto T, Asakura M, Hirata N, Imafuku J, Matsui H, Hasegawa K: Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action. Biol Psychiatry. 1984 Sep;19(9):1283-91. Pubmed 18. Alpha-2B adrenergic receptor Pharmacological action: unknown Actions: antagonist 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 clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol Organism class: human UniProt ID: P18089 Gene: ADRA2B Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Tsukamoto T, Asakura M, Hirata N, Imafuku J, Matsui H, Hasegawa K: Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action. Biol Psychiatry. 1984 Sep;19(9):1283-91. Pubmed 19. Alpha-2C adrenergic receptor Pharmacological action: unknown Actions: antagonist Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins Organism class: human UniProt ID: P18825 Gene: ADRA2C Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed Tsukamoto T, Asakura M, Hirata N, Imafuku J, Matsui H, Hasegawa K: Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action. Biol Psychiatry. 1984 Sep;19(9):1283-91. Pubmed

Targets

1. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out

Gene: DRD2 Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed
Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

2. D(1A) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21728 Link_out

Gene: DRD1 Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed

3. D(1B) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21918 Link_out

Gene: DRD5 Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed

4. D(3) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P35462 Link_out

Gene: DRD3 Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed

5. D(4) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P21917 Link_out

Gene: DRD4 Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed

6. 5-hydroxytryptamine 2A receptor

Pharmacological action: unknown
Actions: antagonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out

Gene: HTR2A Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed

7. 5-hydroxytryptamine 2C receptor

Pharmacological action: unknown
Actions: antagonist

Organism class: human
UniProt ID: P28335 Link_out

Gene: HTR2C Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed

8. Histamine H1 receptor

Pharmacological action: unknown
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:

Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed

9. Muscarinic acetylcholine receptor M1

Pharmacological action: unknown
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:

Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed

10. Muscarinic acetylcholine receptor M2

Pharmacological action: unknown
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:

Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed

11. Muscarinic acetylcholine receptor M3

Pharmacological action: unknown
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:

Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed

12. Muscarinic acetylcholine receptor M4

Pharmacological action: unknown
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:

Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed

13. Muscarinic acetylcholine receptor M5

Pharmacological action: unknown
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:

Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed

14. Alpha-1A adrenergic receptor

Pharmacological action: unknown
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:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed
Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed

15. Alpha-1B adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out

Gene: ADRA1B Link_out

Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed
Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed

16. Alpha-1D adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

Organism class: human
UniProt ID: P25100 Link_out

Gene: ADRA1D Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed
Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed

17. Alpha-2A adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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

Organism class: human
UniProt ID: P08913 Link_out

Gene: ADRA2A Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed
Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Tsukamoto T, Asakura M, Hirata N, Imafuku J, Matsui H, Hasegawa K: Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action. Biol Psychiatry. 1984 Sep;19(9):1283-91. Pubmed

18. Alpha-2B adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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 clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Organism class: human
UniProt ID: P18089 Link_out

Gene: ADRA2B Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed
Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Tsukamoto T, Asakura M, Hirata N, Imafuku J, Matsui H, Hasegawa K: Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action. Biol Psychiatry. 1984 Sep;19(9):1283-91. Pubmed

19. Alpha-2C adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

Organism class: human
UniProt ID: P18825 Link_out

Gene: ADRA2C Link_out

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

References:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed
Dahl SG, Hough E, Hals PA: Phenothiazine drugs and metabolites: molecular conformation and dopaminergic, alpha adrenergic and muscarinic cholinergic receptor binding. Biochem Pharmacol. 1986 Apr 15;35(8):1263-9. Pubmed
Tsukamoto T, Asakura M, Hirata N, Imafuku J, Matsui H, Hasegawa K: Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action. Biol Psychiatry. 1984 Sep;19(9):1283-91. Pubmed

Enzymes
1. Cytochrome P450 2D6 Actions: substrate, inhibitor 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: Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed 2. Cytochrome P450 2E1 Actions: inhibitor Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms UniProt ID: P05181 Gene: CYP2E1 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 3. Cytochrome P450 1A2 Actions: inhibitor 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: Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed

Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

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:

Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2E1

Actions: inhibitor

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out

Gene: CYP2E1 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

3. Cytochrome P450 1A2

Actions: inhibitor

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:

Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. Pubmed

Comments

Drug created on July 10, 2007 12:38 / Updated on April 19, 2011 15:10

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.