Identification
- Generic Name
- Pipamperone
- DrugBank Accession Number
- DB09286
- Background
Pipamperone is a typical antipsychotic of the butyrophenone family used in the treatment of schizophrenia. It was developed by Janssen Pharmaceutica in 1961 and started its first round of clinical trials in 1963 11,15.
In an effort to improve haloperidol's pharmacological effects, Janssen discovered that pipamperone, an agent whose pharmacological profile was distinct from haloperidol and all other known antipsychotic drugs at this time, had significant anti-tryptamine activity. Some studies suggest pipamperone was the first atypical antipsychotic. Interestingly, when risperidone was created, Janssen suggested it was a more potent version of pipamperone. Synthesized in the year 1984, risperidone’s pharmacological properties were similar to pipamperone’s in that both block more serotonin more potently than dopamine 15.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Pipamperone (DB09286)
- Weight
- Average: 375.488
Monoisotopic: 375.232205381 - Chemical Formula
- C21H30FN3O2
- Synonyms
- Carpiperone
- Floropipamide
- Fluoropipamide
- Pipamperona
- Pipamperone
Pharmacology
- Indication
Treatment of chronic psychoses and states of aggressiveness of various origins 12.
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
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Pipamperone is an antipsychotic medication that has sedative effects, which may be beneficial in the management of agitation and disordered sleep 8. Pipamperone, showing antidopaminergic and anti-serotonergic properties, has been noted for its anti- agitation effects and for its ability to normalize sleep rhythms in psychiatric patients 5. One study showed that pipamperone increased the expression of D4 (dopaminergic) receptors, explaining its helpfulness in decreasing positive psychotic symptoms, such as delusions and hallucinations 19.
- Mechanism of action
Pipamperone binds mainly to 5-HT2A receptors, with a nearly equal affinity to D4 receptors and a moderate affinity for 5-HT2C, D2, D3, 1- and 2B-adrenoceptors 5.
This drug is a selective 5-HT2A, D1 and D4 antagonist 13,1. Extrapyramidal adverse effects also appear to be limited in pipamperone treatment compared to traditional antipsychotic medications due to its high receptor selectivity 11.
Pipamperone has a 15-fold higher affinity for D4 than D2 receptors. It has been suggested that D4 receptors may play a role in the modulation of GABAergic neuronal activity by dopamine 5.
Target Actions Organism UDopamine D2 receptor antagonistHumans U5-hydroxytryptamine receptor 2A agonistHumans UAlpha-1 adrenergic receptors antagonistHumans UDopamine D4 receptor antagonistHumans UDopamine D1 receptor antagonistHumans UDopamine D3 receptor Not Available Humans U5-hydroxytryptamine receptor 2B Not Available Humans UAlpha-2A adrenergic receptor antagonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Pipamperone is metabolised in the liver 11.
- Route of elimination
Mainly via the kidneys 11
- Half-life
17-26h 18
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Ld50 in rats, 48 mg/kg 16. Prolonged Qtc interval. Monitoring with regular ECGs is recommended 20.
- Pathways
- Not Available
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Pipamperone is combined with 1,2-Benzodiazepine. Abaloparatide The risk or severity of adverse effects can be increased when Abaloparatide is combined with Pipamperone. Acebutolol The risk or severity of adverse effects can be increased when Acebutolol is combined with Pipamperone. Acenocoumarol The risk or severity of adverse effects can be increased when Pipamperone is combined with Acenocoumarol. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Pipamperone. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Pipamperone. Agomelatine The risk or severity of CNS depression can be increased when Agomelatine is combined with Pipamperone. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Pipamperone. Alfentanil The risk or severity of CNS depression can be increased when Alfentanil is combined with Pipamperone. Alimemazine The risk or severity of CNS depression can be increased when Alimemazine is combined with Pipamperone. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - 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 Pipamperone hydrochloride IT085U64JB 2448-68-2 BMXXSXQVMCXGJM-UHFFFAOYSA-N - International/Other Brands
- Dipiperon / Propitan
Categories
- ATC Codes
- N05AD05 — Pipamperone
- Drug Categories
- Antidepressive Agents
- Antipsychotic Agents
- Butyrophenone Derivatives
- Central Nervous System Agents
- Central Nervous System Depressants
- Dopamine Antagonists
- Dopamine D2 Receptor Antagonists
- Hypotensive Agents
- Ketones
- Nervous System
- Neurotoxic agents
- Neurotransmitter Agents
- Psycholeptics
- Psychotropic Drugs
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin Receptor Antagonists
- Tranquilizing Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbonyl compounds
- Direct Parent
- Alkyl-phenylketones
- Alternative Parents
- Phenylbutylamines / Butyrophenones / Piperidinecarboxamides / Aryl alkyl ketones / Benzoyl derivatives / Aminopiperidines / Fluorobenzenes / Aryl fluorides / Gamma-amino ketones / Trialkylamines show 6 more
- Substituents
- 4-aminopiperidine / Alkyl-phenylketone / Amine / Aromatic heteromonocyclic compound / Aryl alkyl ketone / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Benzoyl show 20 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- organofluorine compound, tertiary amino compound, monocarboxylic acid amide, aromatic ketone, bipiperidines (CHEBI:78549)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 5402501F0W
- CAS number
- 1893-33-0
- InChI Key
- AXKPFOAXAHJUAG-UHFFFAOYSA-N
- InChI
- InChI=1S/C21H30FN3O2/c22-18-8-6-17(7-9-18)19(26)5-4-12-24-15-10-21(11-16-24,20(23)27)25-13-2-1-3-14-25/h6-9H,1-5,10-16H2,(H2,23,27)
- IUPAC Name
- 1'-[4-(4-fluorophenyl)-4-oxobutyl]-[1,4'-bipiperidine]-4'-carboxamide
- SMILES
- NC(=O)C1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)N1CCCCC1
References
- General References
- Prinssen EP, Koek W, Kleven MS: The effects of antipsychotics with 5-HT(2C) receptor affinity in behavioral assays selective for 5-HT(2C) receptor antagonist properties of compounds. Eur J Pharmacol. 2000 Jan 24;388(1):57-67. [Article]
- Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL: Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences. J Pharmacol Exp Ther. 1996 Feb;276(2):720-7. [Article]
- Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [Article]
- Wade AG, Crawford GM, Nemeroff CB, Schatzberg AF, Schlaepfer T, McConnachie A, Haazen L, Buntinx E: Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response. Psychol Med. 2011 Oct;41(10):2089-97. doi: 10.1017/S0033291711000158. Epub 2011 Feb 25. [Article]
- Gareri P, De Fazio P, Stilo M, Ferreri G, De Sarro G: Conventional and atypical antipsychotics in the elderly : a review. Clin Drug Investig. 2003;23(5):287-322. [Article]
- Van Craenenbroeck K, Gellynck E, Lintermans B, Leysen JE, Van Tol HH, Haegeman G, Vanhoenacker P: Influence of the antipsychotic drug pipamperone on the expression of the dopamine D4 receptor. Life Sci. 2006 Dec 3;80(1):74-81. doi: 10.1016/j.lfs.2006.08.024. Epub 2006 Aug 25. [Article]
- Wijma RA, van der Nagel BC, Dierckx B, Dieleman GC, Touw DJ, van Gelder T, Koch BC: Identification and quantification of the antipsychotics risperidone, aripiprazole, pipamperone and their major metabolites in plasma using ultra-high performance liquid chromatography-mass spectrometry. Biomed Chromatogr. 2016 Jun;30(6):794-801. doi: 10.1002/bmc.3610. Epub 2015 Oct 8. [Article]
- Squelart P, Saravia J: Pipamperone (Dipiperon), a useful sedative neuroleptic drug in troublesome chronic psychotic patients. Acta Psychiatr Belg. 1977 Mar-Apr;77(2):284-93. [Article]
- Pipamperone [Link]
- The Treatment of Autism with Pipamperone [Link]
- Pipamperone [Link]
- Pipamperone: International drug information [Link]
- Low dose pipamperone in treatment mood disorders [Link]
- Pipamperone dihydrochloride [Link]
- The Pharmacological Role and Clinical Applications of Antipsychotics’ Active Metabolites: Paliperidone versus Risperidone [Link]
- Pipamerone [Link]
- Pipamperone and increased excercise/weight [Link]
- Current antipsychotics [Link]
- Use of pipamperone and a d2-receptor antagonist or a serotonin/dopamin antagonist for the treatment of psychotic disorders [Link]
- PP232—Acute toxicity profile of pipamperone in overdose: A consecutive case series [Link]
- External Links
- KEGG Drug
- D02622
- PubChem Compound
- 4830
- PubChem Substance
- 310265179
- ChemSpider
- 4664
- BindingDB
- 81483
- 33739
- ChEBI
- 78549
- ChEMBL
- CHEMBL440294
- ZINC
- ZINC000021297287
- Wikipedia
- Pipamperone
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Major Depressive Disorder (MDD) 1 3 Terminated Treatment Anxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia 1 2 Completed Treatment Chronic Schizophrenia / Schizoaffective Disorders 1 2 Completed Treatment Depression 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) >254 https://www.trc-canada.com/product-detail/?P475200 water solubility soluble in methanol https://www.trc-canada.com/product-detail/?P475200 logP 2.02 https://comptox.epa.gov/dashboard/dsstoxdb/results?search=Pipamperone - Predicted Properties
Property Value Source Water Solubility 0.182 mg/mL ALOGPS logP 2.32 ALOGPS logP 1.87 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 15.94 Chemaxon pKa (Strongest Basic) 8.69 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 66.64 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 105.1 m3·mol-1 Chemaxon Polarizability 41.16 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- 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
- Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [Article]
- Kind
- Protein group
- 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...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-1A adrenergic receptor | P35348 |
| Alpha-1B adrenergic receptor | P35368 |
| Alpha-1D adrenergic receptor | P25100 |
References
- Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
- Gene Name
- HTR2B
- Uniprot ID
- P41595
- Uniprot Name
- 5-hydroxytryptamine receptor 2B
- Molecular Weight
- 54297.41 Da
- Kind
- Protein
- Organism
- Humans
- 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
- Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [Article]
Drug created at October 29, 2015 18:11 / Updated at February 03, 2022 06:26