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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2021-09-14 14:59:19 UTC
HMDB IDHMDB0015474
Secondary Accession Numbers
  • HMDB15474
Metabolite Identification
Common NameMethotrimeprazine
DescriptionMethotrimeprazine, also known as levomepromazine or tisercin, 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. As is typical of phenothiazine antipsychotics, levomepromazine is a "dirty drug", that is, it exerts its effects by blocking a variety of receptors, including adrenergic receptors, dopamine receptors, histamine receptors, muscarinic acetylcholine receptors and serotonin receptors. Methotrimeprazine is a drug which is used for the treatment of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder. Levomepromazine is frequently prescribed and valued worldwide in palliative care medicine for its multimodal action, to treat intractable nausea or vomiting, and for severe delirium/agitation in the last days of life. Methotrimeprazine is a very strong basic compound (based on its pKa). Methotrimeprazine is a potentially toxic compound. Serious side effects include tardive dyskinesia, akathisia, abnormalities in the electrical cycle of the heart, low blood pressure and the potentially fatal neuroleptic malignant syndrome. Brand names include Nozinan, Levoprome, Detenler, Hirnamin, Levotomin and Neurocil. Palliative care physicians will commonly prescribe it orally or via subcutaneous syringe drivers in combination with opioid analgesics such as hydromorphone. A 2010 systematic review compared the efficacy of levomepromazine with atypical antipsychotic drugs:The most common side effect is akathisia. Levomepromazine is used for the treatment of psychosis, particularly those of schizophrenia, and manic phases of bipolar disorder. In any case, blood pressure and EKG should be monitored regularly. A rare but life-threatening side effect is neuroleptic malignant syndrome (NMS).
Structure
Data?1582753300
Synonyms
ValueSource
(-)-(2R)-3-(2-Methoxy-10H-phenothiazin-10-yl)-N,N,2-trimethylpropan-1-amineChEBI
(-)-10-(3-(Dimethylamino)-2-methylpropyl)-2-methoxyphenothiazineChEBI
2-MethoxytrimeprazineChEBI
LevomepromazinaChEBI
LevomepromazineChEBI
LevomepromazinumChEBI
LevopromeKegg
LevopromazineHMDB
TisercinHMDB
LevomeprazinHMDB
TizertsinHMDB
TizercineHMDB
Chemical FormulaC19H24N2OS
Average Molecular Weight328.472
Monoisotopic Molecular Weight328.16093409
IUPAC Name[(2R)-3-(2-methoxy-10H-phenothiazin-10-yl)-2-methylpropyl]dimethylamine
Traditional Namemethotrimeprazine
CAS Registry Number60-99-1
SMILES
COC1=CC2=C(SC3=C(C=CC=C3)N2C[C@H](C)CN(C)C)C=C1
InChI Identifier
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
InChI KeyVRQVVMDWGGWHTJ-CQSZACIVSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • Aryl thioether
  • Anisole
  • Tertiary aliphatic/aromatic amine
  • Alkyl aryl ether
  • Para-thiazine
  • Benzenoid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ether
  • Azacycle
  • Thioether
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0052 g/LNot Available
LogP4.68HANSCH,C ET AL. (1995)
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.0052 g/LALOGPS
logP4.84ALOGPS
logP4.25ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)9.42ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area15.71 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity99.83 m³·mol⁻¹ChemAxon
Polarizability36.77 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Spectral Properties

Collision Cross Sections

NameAdductTypeData SourceValueReference
DarkChem[M+H]+PredictedNot Available175.74231661259
DarkChem[M-H]-PredictedNot Available176.9331661259

Retention Indices

Underivatized

Not Available

Derivatized

Not Available
Spectra

GC-MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9272000000-663ed1e564555c7e8fae2017-09-01View Spectrum
MSMass Spectrum (Electron Ionization)splash10-056r-9356000000-bb17e4980980d336d3372014-09-20View Spectrum

LC-MS/MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-004i-0009000000-292add600a1d733c36622017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-004i-0319000000-9bcdb870e16f29c42cc72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-2920000000-f73fff6b08acc61ea5b72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0zfr-6920000000-dc5968beb0d112813d552017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0a4i-9410000000-0d1f6734452bedc68d3f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-0udi-0910000000-10fe32fa41981fcda6522017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0469000000-698db513d68f8238a2842016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ue9-3983000000-0963d25ff0f442a1b8192016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pc3-9420000000-45332e32eecba186d7002016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0019000000-783dfd7af7ab08cc73372016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00p0-0494000000-78a58d14f5fb19218ba82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002b-3960000000-d1127cf211de0694b9522016-08-03View Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01403 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01403 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01403
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID65239
KEGG Compound IDC07192
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLevomepromazine
METLIN IDNot Available
PubChem Compound72287
PDB IDNot Available
ChEBI ID6838
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Doctissimo [Link]

Only showing the first 10 proteins. There are 22 proteins in total.

Enzymes

General function:
Involved in monooxygenase 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 or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular weight:
56848.42
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 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular weight:
48956.3
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 > 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
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular weight:
49953.1
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
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
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular weight:
50618.9
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
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
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular weight:
48359.9
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. 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
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular weight:
51820.7
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular weight:
55783.6
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 ]

Only showing the first 10 proteins. There are 22 proteins in total.