Identification

Name
Methotrimeprazine
Accession Number
DB01403
Type
Small Molecule
Groups
Approved, Investigational
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
Thumb
Synonyms
  • (-)-(2R)-3-(2-Methoxy-10H-phenothiazin-10-yl)-N,N,2-trimethylpropan-1-amine
  • (-)-10-(3-(Dimethylamino)-2-methylpropyl)-2-methoxyphenothiazine
  • 2-Methoxytrimeprazine
  • Levomepromazina
  • Levomepromazine
  • Levomepromazinum
  • Methotrimeprazine
External IDs
CL 36467 / CL 39743 / N05AA02 / RP 7044 / RP-7044 / SK&F 5116 / XP-03 / XP03
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MethoprazineTablet25 mgOralAa Pharma Inc1998-07-20Not applicableCanada
MethoprazineTablet5 mgOralAa Pharma Inc1998-07-20Not applicableCanada
MethoprazineTablet50 mgOralAa Pharma Inc1998-07-20Not applicableCanada
MethoprazineTablet2 mgOralAa Pharma Inc1998-07-20Not applicableCanada
Methotrimeprazine-2Tablet2 mgOralPro Doc Limitee1999-05-102009-07-23Canada
Methotrimeprazine-25Tablet25 mgOralPro Doc Limitee1999-05-122011-07-27Canada
Methotrimeprazine-5Tablet5 mgOralPro Doc Limitee1999-05-122011-07-27Canada
Methotrimeprazine-50Tablet50 mgOralPro Doc Limitee1999-05-102011-07-27Canada
Nov Meprazine Tab 50mgTablet50 mgOralNovopharm Limited1996-12-312005-08-10Canada
Novo Meprazine Tab 25mgTablet25 mgOralNovopharm Limited1996-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PMS-methotrimeprazineTablet5 mgOralPharmascience Inc1997-10-20Not applicableCanada
PMS-methotrimeprazineTablet50 mgOralPharmascience Inc1997-10-20Not applicableCanada
PMS-methotrimeprazineTablet25 mgOralPharmascience Inc1997-10-20Not applicableCanada
Riva-meprazine 25mg TabletsTablet25 mgOralLaboratoire Riva Inc1999-11-222003-07-28Canada
Riva-meprazine 50mg TabletsTablet50 mgOralLaboratoire Riva Inc1999-11-222003-07-28Canada
Riva-meprazine 5mg TabletsTablet5 mgOralLaboratoire Riva Inc1999-11-222003-07-28Canada
International/Other Brands
Levoprome / Neurocil / Nosinan / Nozinan
Categories
UNII
9G0LAW7ATQ
CAS number
60-99-1
Weight
Average: 328.472
Monoisotopic: 328.16093409
Chemical Formula
C19H24N2OS
InChI Key
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
IUPAC Name
[(2R)-3-(2-methoxy-10H-phenothiazin-10-yl)-2-methylpropyl]dimethylamine
SMILES
COC1=CC2=C(SC3=C(C=CC=C3)N2C[C@H](C)CN(C)C)C=C1

Pharmacology

Indication

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

Associated Conditions
Associated Therapies
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.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
UD(1A) dopamine receptor
antagonist
Human
UD(1B) dopamine receptor
antagonist
Human
UD(3) dopamine receptor
antagonist
Human
UD(4) dopamine receptor
antagonist
Human
U5-hydroxytryptamine receptor 2A
antagonist
Human
U5-hydroxytryptamine receptor 2C
antagonist
Human
UHistamine H1 receptor
antagonist
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
UMuscarinic acetylcholine receptor M4
antagonist
Human
UMuscarinic acetylcholine receptor M5
antagonist
Human
UAlpha-1A adrenergic receptor
antagonist
Human
UAlpha-1B adrenergic receptor
antagonist
Human
UAlpha-1D adrenergic receptor
antagonist
Human
UAlpha-2A adrenergic receptor
antagonist
Human
UAlpha-2B adrenergic receptor
antagonist
Human
UAlpha-2C adrenergic receptor
antagonist
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe risk or severity of adverse effects can be increased when Methotrimeprazine is combined with (2-benzhydryloxyethyl)diethyl-methylammonium iodide.
(R)-warfarinThe risk or severity of adverse effects can be increased when Methotrimeprazine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Methotrimeprazine is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of Methotrimeprazine can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Methotrimeprazine.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Methotrimeprazine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Methotrimeprazine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Methotrimeprazine is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
7-Nitroindazole7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
Food Interactions
  • Take with food to reduce irritation.

References

Synthesis Reference

Christian Berger, "Process for preparing levomepromazine hydrogen maleate." U.S. Patent US4798895, issued January 17, 1989.

US4798895
General References
  1. Link [Link]
External Links
Human Metabolome Database
HMDB0015474
KEGG Drug
D00403
KEGG Compound
C07192
PubChem Compound
72287
PubChem Substance
46507223
ChemSpider
65239
BindingDB
50418049
ChEBI
6838
ChEMBL
CHEMBL1764
PharmGKB
PA164743234
Wikipedia
Levomepromazine
ATC Codes
N05AA02 — Levomepromazine
AHFS Codes
  • 28:16.08.24 — Phenothiazines

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentPsychosis Nos/Other1
Not AvailableActive Not RecruitingTreatmentSchizophrenia Relapse1
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral2 mg
TabletOral25 mg
TabletOral5 mg
TabletOral50 mg
SolutionOral5 mg
SolutionIntramuscular; Intravenous25 mg
Liquid; solution / dropsOral40 mg
Prices
Unit descriptionCostUnit
Nozinan 25 mg/ml3.6USD ml
Apo-Methoprazine 50 mg Tablet0.4USD tablet
Apo-Methoprazine 25 mg Tablet0.27USD tablet
Apo-Methoprazine 5 mg Tablet0.1USD tablet
Apo-Methoprazine 2 mg Tablet0.07USD 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
water solubility20 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.68HANSCH,C ET AL. (1995)
logS-4.22ADME Research, USCD
pKa9.19SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.00525 mg/mLALOGPS
logP4.84ALOGPS
logP4.25ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)9.42ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area15.71 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity99.83 m3·mol-1ChemAxon
Polarizability36.77 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9857
Blood Brain Barrier+0.9935
Caco-2 permeable+0.6694
P-glycoprotein substrateSubstrate0.6805
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IIInhibitor0.8571
Renal organic cation transporterNon-inhibitor0.5132
CYP450 2C9 substrateNon-substrate0.7511
CYP450 2D6 substrateSubstrate0.5363
CYP450 3A4 substrateSubstrate0.6056
CYP450 1A2 substrateInhibitor0.6953
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.5432
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5633
Ames testNon AMES toxic0.5562
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5064 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.932
hERG inhibition (predictor II)Inhibitor0.8488
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)MSsplash10-056r-9356000000-bb17e4980980d336d337
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-QQ , positiveLC-MS/MSsplash10-004i-0009000000-292add600a1d733c3662
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004i-0319000000-9bcdb870e16f29c42cc7
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-2920000000-f73fff6b08acc61ea5b7
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0zfr-6920000000-dc5968beb0d112813d55
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-9410000000-0d1f6734452bedc68d3f
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0udi-0910000000-10fe32fa41981fcda652

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / Anisoles / Alkyl aryl ethers / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Anisole / Tertiary aliphatic/aromatic amine / Alkyl aryl ether / Para-thiazine / Benzenoid / Tertiary aliphatic amine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, tertiary amine (CHEBI:6838)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
  2. 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:2870716]
  3. 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:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD5
Uniprot ID
P21918
Uniprot Name
D(1B) dopamine receptor
Molecular Weight
52950.5 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Sh3 domain binding
Specific Function
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name
DRD4
Uniprot ID
P21917
Uniprot Name
D(4) dopamine receptor
Molecular Weight
48359.86 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. 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:2899826]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. 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:2870716]
  2. 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:2899826]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. 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:2870716]
  2. 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:2899826]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. 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:2870716]
  2. 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:2899826]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. 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:2870716]
  2. 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:2899826]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. 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:2870716]
  2. 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:2899826]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
  2. 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:2870716]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
  2. 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:2870716]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
  2. 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:2870716]
Kind
Protein
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...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
  2. 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:2870716]
  3. 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:6149771]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Epinephrine 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 clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
  2. 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:2870716]
  3. 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:6149771]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Green B, Pettit T, Faith L, Seaton K: Focus on levomepromazine. Curr Med Res Opin. 2004 Dec;20(12):1877-81. [PubMed:15701205]
  2. 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:2870716]
  3. 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:6149771]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Yoshimura R, Ueda N, Nakamura J: Low dosage of levomepromazine did not increase plasma concentrations of fluvoxamine. Int Clin Psychopharmacol. 2000 Jul;15(4):233-5. [PubMed:10954064]
  3. Yukawa E, Hokazono T, Yukawa M, Ichimaru R, Maki T, Matsunaga K, Ohdo S, Anai M, Higuchi S, Goto Y: Population pharmacokinetics of haloperidol using routine clinical pharmacokinetic data in Japanese patients. Clin Pharmacokinet. 2002;41(2):153-9. doi: 10.2165/00003088-200241020-00006. [PubMed:11888334]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 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]

Drug created on July 10, 2007 12:38 / Updated on October 21, 2018 20:31