Propiomazine

Identification

Name
Propiomazine
Accession Number
DB00777
Description

Propiomazine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, propiomazine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 340.482
Monoisotopic: 340.16093409
Chemical Formula
C20H24N2OS
Synonyms
  • 10-(2-Dimethylaminopropyl)-2-propionylphenothiazine
  • 2-Propionyl-10-(2-(dimethylamino)propyl)phenothiazine
  • 3-Propionyl-10-dimethylaminoisopropylphenothiazine
  • Propiomazin
  • Propiomazina
  • Propiomazine
  • Propiomazinum
External IDs
  • CB 1678
  • Wy 1359

Pharmacology

Indication

Propiomazine is largely used for its antihistamininc sleep inducing effects in treating insomnia.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Although propiomazine is a phenothiazine, it is not used as an antipsychotic. It posesses antihistamine effects and is mostly used as a sedative in treating insomnia.

Mechanism of action

Propiomazine acts as an antagonist of dopamine 1, 2, and 4 receptors, serotonin (5-HT) receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Its main use as a sedative is due to its antihistamine effect.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Humans
UMuscarinic acetylcholine receptor
antagonist
Humans
UAlpha-1A adrenergic receptor
antagonist
Humans
UDopamine D2 receptor
antagonist
Humans
U5-hydroxytryptamine receptor 2A
antagonist
Humans
U5-hydroxytryptamine receptor 2C
antagonist
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

81%

Metabolism

Unknown, but most likely hepatic as with other phenothiazines.

Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Although rare, serious adverse events may be seen with propiomazine. Such events include convulsions (seizures), difficult or unusually fast breathing, fast or irregular heartbeat or pulse, fever (high), high or low blood pressure, loss of bladder control, muscle stiffness (severe), unusual increase in sweating, unusually pale skin, and unusual tiredness or weakness.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Propiomazine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Propiomazine.
AceclofenacThe risk or severity of hypertension can be increased when Propiomazine is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Propiomazine is combined with Acemetacin.
AcenocoumarolThe risk or severity of adverse effects can be increased when Propiomazine is combined with Acenocoumarol.
AcetazolamideAcetazolamide may increase the central nervous system depressant (CNS depressant) activities of Propiomazine.
AcetophenazineAcetophenazine may increase the central nervous system depressant (CNS depressant) activities of Propiomazine.
Acetylsalicylic acidThe risk or severity of hypertension can be increased when Propiomazine is combined with Acetylsalicylic acid.
AclidiniumThe risk or severity of adverse effects can be increased when Propiomazine is combined with Aclidinium.
AdenosineThe risk or severity of Tachycardia can be increased when Adenosine is combined with Propiomazine.
AgomelatineThe risk or severity of adverse effects can be increased when Propiomazine is combined with Agomelatine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not Available

Products

Product Ingredients
IngredientUNIICASInChI Key
Propiomazine hydrochloride70BO17YR031240-15-9UGVNGSMLNPWNNA-UHFFFAOYSA-N
International/Other Brands
Dorevan / Dorevane / Indorm / Largon / Propavan (Sanofi-Aventis) / Serentin

Categories

ATC Codes
N05CM06 — Propiomazine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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 / Aryl alkyl ketones / Benzenoids / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Alkyldiarylamine / Amine / Aromatic heteropolycyclic compound / Aryl alkyl ketone / Aryl ketone / Aryl thioether / Azacycle / Benzenoid / Diarylthioether / Hydrocarbon derivative
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, tertiary amino compound, aromatic ketone (CHEBI:8491)

Chemical Identifiers

UNII
242Z0PM79Y
CAS number
362-29-8
InChI Key
UVOIBTBFPOZKGP-UHFFFAOYSA-N
InChI
InChI=1S/C20H24N2OS/c1-5-18(23)15-10-11-20-17(12-15)22(13-14(2)21(3)4)16-8-6-7-9-19(16)24-20/h6-12,14H,5,13H2,1-4H3
IUPAC Name
1-{10-[2-(dimethylamino)propyl]-10H-phenothiazin-2-yl}propan-1-one
SMILES
CCC(=O)C1=CC2=C(SC3=CC=CC=C3N2CC(C)N(C)C)C=C1

References

General References
Not Available
Human Metabolome Database
HMDB0014915
KEGG Drug
D02361
KEGG Compound
C07405
PubChem Compound
4940
PubChem Substance
46506205
ChemSpider
4771
RxNav
8770
ChEBI
8491
ChEMBL
CHEMBL1201210
Therapeutic Targets Database
DAP000327
PharmGKB
PA164778685
Wikipedia
Propiomazine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Hr cenci laboratories inc
  • Baxter healthcare corp anesthesia critical care
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility0.454 mg/LNot Available
logP4.79BIOBYTE (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.00703 mg/mLALOGPS
logP4.53ALOGPS
logP4.55ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)16.64ChemAxon
pKa (Strongest Basic)8.32ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area23.55 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity103.53 m3·mol-1ChemAxon
Polarizability38.62 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.996
Blood Brain Barrier+0.9837
Caco-2 permeable+0.796
P-glycoprotein substrateSubstrate0.8544
P-glycoprotein inhibitor IInhibitor0.9338
P-glycoprotein inhibitor IINon-inhibitor0.7772
Renal organic cation transporterNon-inhibitor0.5594
CYP450 2C9 substrateNon-substrate0.8106
CYP450 2D6 substrateSubstrate0.7113
CYP450 3A4 substrateSubstrate0.5966
CYP450 1A2 substrateInhibitor0.8364
CYP450 2C9 inhibitorNon-inhibitor0.8827
CYP450 2D6 inhibitorInhibitor0.7359
CYP450 2C19 inhibitorNon-inhibitor0.8787
CYP450 3A4 inhibitorNon-inhibitor0.7492
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5182
Ames testNon AMES toxic0.8431
CarcinogenicityNon-carcinogens0.8384
BiodegradationNot ready biodegradable0.993
Rat acute toxicity2.7773 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9731
hERG inhibition (predictor II)Inhibitor0.6987
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.28 KB)
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - EI-BGC-MSsplash10-00di-9100000000-976e369803cbbc61ad7a
Mass Spectrum (Electron Ionization)MSsplash10-00di-9220000000-31dfa9c2a3e2a6046ef7
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

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
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. KRAKOWSKI AJ: Propiomazine for control of insomnia in nervous disorders. Am J Psychiatry. 1962 Nov;119:461-2. [PubMed:14035428]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Kim DH, Maneen MJ, Stahl SM: Building a better antipsychotic: receptor targets for the treatment of multiple symptom dimensions of schizophrenia. Neurotherapeutics. 2009 Jan;6(1):78-85. doi: 10.1016/j.nurt.2008.10.020. [PubMed:19110200]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Little direct evidence is available for propiomazine's specific mechanism of action. However, it structural and pharmacological similarity to promethazine helps elucidate some of its effects at these targets. The evidence largely points to M1 receptor interactions, though there is potential for activity at other muscarinic receptors.
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...

Components:
References
  1. Kim DH, Maneen MJ, Stahl SM: Building a better antipsychotic: receptor targets for the treatment of multiple symptom dimensions of schizophrenia. Neurotherapeutics. 2009 Jan;6(1):78-85. doi: 10.1016/j.nurt.2008.10.020. [PubMed:19110200]
  2. Page CB, Duffull SB, Whyte IM, Isbister GK: Promethazine overdose: clinical effects, predicting delirium and the effect of charcoal. QJM. 2009 Feb;102(2):123-31. doi: 10.1093/qjmed/hcn153. Epub 2008 Nov 28. [PubMed:19042969]
  3. Sharma A, Hamelin BA: Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view. Curr Drug Metab. 2003 Apr;4(2):105-29. doi: 10.2174/1389200033489523. [PubMed:12678691]
  4. POWE CE, KIEM IM, FROMHAGEN C, CAVANAGH D: Propiomazine hydrochloride in obstetrical analgesia. A controlled study of 520 patients. JAMA. 1962 Jul 28;181:290-4. doi: 10.1001/jama.1962.03050300010002. [PubMed:14488364]
Kind
Protein
Organism
Humans
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. Kim DH, Maneen MJ, Stahl SM: Building a better antipsychotic: receptor targets for the treatment of multiple symptom dimensions of schizophrenia. Neurotherapeutics. 2009 Jan;6(1):78-85. doi: 10.1016/j.nurt.2008.10.020. [PubMed:19110200]
  2. POWE CE, KIEM IM, FROMHAGEN C, CAVANAGH D: Propiomazine hydrochloride in obstetrical analgesia. A controlled study of 520 patients. JAMA. 1962 Jul 28;181:290-4. doi: 10.1001/jama.1962.03050300010002. [PubMed:14488364]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Little direct evidence is available for propiomazine's specific mechanism of action. However, it structural and pharmacological similarity to promethazine helps elucidate some of its effects at this target.
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. Strange PG: Antipsychotic drug action: antagonism, inverse agonism or partial agonism. Trends Pharmacol Sci. 2008 Jun;29(6):314-21. doi: 10.1016/j.tips.2008.03.009. Epub 2008 May 28. [PubMed:18471899]
  2. Kim DH, Maneen MJ, Stahl SM: Building a better antipsychotic: receptor targets for the treatment of multiple symptom dimensions of schizophrenia. Neurotherapeutics. 2009 Jan;6(1):78-85. doi: 10.1016/j.nurt.2008.10.020. [PubMed:19110200]
  3. Adolph O, Koster S, Georgieff M, Georgieff EM, Moulig W, Fohr KJ: Promethazine inhibits NMDA-induced currents - new pharmacological aspects of an old drug. Neuropharmacology. 2012 Aug;63(2):280-91. doi: 10.1016/j.neuropharm.2012.03.006. Epub 2012 Apr 7. [PubMed:22507664]
Kind
Protein
Organism
Humans
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. Kim DH, Maneen MJ, Stahl SM: Building a better antipsychotic: receptor targets for the treatment of multiple symptom dimensions of schizophrenia. Neurotherapeutics. 2009 Jan;6(1):78-85. doi: 10.1016/j.nurt.2008.10.020. [PubMed:19110200]
  2. Sharma A, Hamelin BA: Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view. Curr Drug Metab. 2003 Apr;4(2):105-29. doi: 10.2174/1389200033489523. [PubMed:12678691]
  3. Adolph O, Koster S, Georgieff M, Georgieff EM, Moulig W, Fohr KJ: Promethazine inhibits NMDA-induced currents - new pharmacological aspects of an old drug. Neuropharmacology. 2012 Aug;63(2):280-91. doi: 10.1016/j.neuropharm.2012.03.006. Epub 2012 Apr 7. [PubMed:22507664]
  4. POWE CE, KIEM IM, FROMHAGEN C, CAVANAGH D: Propiomazine hydrochloride in obstetrical analgesia. A controlled study of 520 patients. JAMA. 1962 Jul 28;181:290-4. doi: 10.1001/jama.1962.03050300010002. [PubMed:14488364]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Little direct evidence is available for propiomazine's specific mechanism of action. However, it structural and pharmacological similarity to promethazine helps elucidate some of its effects at this target.
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. Kim DH, Maneen MJ, Stahl SM: Building a better antipsychotic: receptor targets for the treatment of multiple symptom dimensions of schizophrenia. Neurotherapeutics. 2009 Jan;6(1):78-85. doi: 10.1016/j.nurt.2008.10.020. [PubMed:19110200]
  2. Sharma A, Hamelin BA: Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view. Curr Drug Metab. 2003 Apr;4(2):105-29. doi: 10.2174/1389200033489523. [PubMed:12678691]
  3. Adolph O, Koster S, Georgieff M, Georgieff EM, Moulig W, Fohr KJ: Promethazine inhibits NMDA-induced currents - new pharmacological aspects of an old drug. Neuropharmacology. 2012 Aug;63(2):280-91. doi: 10.1016/j.neuropharm.2012.03.006. Epub 2012 Apr 7. [PubMed:22507664]

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

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