Identification
- Generic Name
- Propiomazine
- DrugBank Accession Number
- DB00777
- Background
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
Structure for Propiomazine (DB00777)
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism AHistamine H1 receptor antagonistHumans UMuscarinic acetylcholine receptor antagonistHumans UAlpha-1A adrenergic receptor antagonistHumans UDopamine D2 receptor antagonistHumans U5-hydroxytryptamine receptor 2A antagonistHumans U5-hydroxytryptamine receptor 2C antagonistHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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.
- Pathways
Pathway Category Propiomazine H1-Antihistamine Action Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Propiomazine is combined with 1,2-Benzodiazepine. Acebutolol Acebutolol may increase the orthostatic hypotensive activities of Propiomazine. Aceclofenac The risk or severity of hypertension can be increased when Propiomazine is combined with Aceclofenac. Acemetacin The risk or severity of hypertension can be increased when Propiomazine is combined with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Propiomazine is combined with Acenocoumarol. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Propiomazine hydrochloride 70BO17YR03 1240-15-9 UGVNGSMLNPWNNA-UHFFFAOYSA-N - International/Other Brands
- Dorevan / Dorevane / Indorm / Largon / Propavan (Sanofi-Aventis) / Serentin
Categories
- ATC Codes
- N05CM06 — Propiomazine
- Drug Categories
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents producing tachycardia
- Agents that produce hypertension
- Anticholinergic Agents
- Antidepressive Agents
- Central Nervous System Depressants
- Dopamine Antagonists
- Dopamine D2 Receptor Antagonists
- Heterocyclic Compounds, Fused-Ring
- Histamine Antagonists
- Histamine H1 Antagonists
- Hypnotics and Sedatives
- Muscarinic Antagonists
- Nervous System
- Psycholeptics
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin 5-HT2C Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Antagonists
- Sulfur Compounds
- 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)
- Affected organisms
- Humans and other mammals
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
- External Links
- Human Metabolome Database
- HMDB0014915
- KEGG Drug
- D02361
- KEGG Compound
- C07405
- PubChem Compound
- 4940
- PubChem Substance
- 46506205
- ChemSpider
- 4771
- 8770
- ChEBI
- 8491
- ChEMBL
- CHEMBL1201210
- Therapeutic Targets Database
- DAP000327
- PharmGKB
- PA164778685
- Wikipedia
- Propiomazine
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
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
Property Value Source water solubility 0.454 mg/L Not Available logP 4.79 BIOBYTE (1995) - Predicted Properties
Property Value Source Water Solubility 0.00703 mg/mL ALOGPS logP 4.53 ALOGPS logP 4.55 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 16.76 Chemaxon pKa (Strongest Basic) 8.92 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 23.55 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 103.53 m3·mol-1 Chemaxon Polarizability 38.62 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.996 Blood Brain Barrier + 0.9837 Caco-2 permeable + 0.796 P-glycoprotein substrate Substrate 0.8544 P-glycoprotein inhibitor I Inhibitor 0.9338 P-glycoprotein inhibitor II Non-inhibitor 0.7772 Renal organic cation transporter Non-inhibitor 0.5594 CYP450 2C9 substrate Non-substrate 0.8106 CYP450 2D6 substrate Substrate 0.7113 CYP450 3A4 substrate Substrate 0.5966 CYP450 1A2 substrate Inhibitor 0.8364 CYP450 2C9 inhibitor Non-inhibitor 0.8827 CYP450 2D6 inhibitor Inhibitor 0.7359 CYP450 2C19 inhibitor Non-inhibitor 0.8787 CYP450 3A4 inhibitor Non-inhibitor 0.7492 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5182 Ames test Non AMES toxic 0.8431 Carcinogenicity Non-carcinogens 0.8384 Biodegradation Not ready biodegradable 0.993 Rat acute toxicity 2.7773 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9731 hERG inhibition (predictor II) Inhibitor 0.6987
Spectra
- Mass Spec (NIST)
- Download (7.28 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 198.7103496 predictedDarkChem Lite v0.1.0 [M-H]- 180.69049 predictedDeepCCS 1.0 (2019) [M+H]+ 199.4975496 predictedDarkChem Lite v0.1.0 [M+H]+ 183.0485 predictedDeepCCS 1.0 (2019) [M+Na]+ 198.4166496 predictedDarkChem Lite v0.1.0 [M+Na]+ 189.85255 predictedDeepCCS 1.0 (2019)
Targets
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- 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
- KRAKOWSKI AJ: Propiomazine for control of insomnia in nervous disorders. Am J Psychiatry. 1962 Nov;119:461-2. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:54