PIPAMPERONE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H30FN3O2.2ClH
Molecular Weight	448.402
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.NC(=O)C1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)N3CCCCC3

InChI

InChIKey=BMXXSXQVMCXGJM-UHFFFAOYSA-N

InChI=1S/C21H30FN3O2.2ClH/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);2*1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C21H30FN3O2
Molecular Weight	375.4802
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB09286
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/14451236 | https://www.ncbi.nlm.nih.gov/pubmed/21349239 | https://www.ncbi.nlm.nih.gov/pubmed/11672571 | https://www.ncbi.nlm.nih.gov/pubmed/8935801 | http://www.onmeda.fr/medicament/dipiperon-93032319.html

Pipamperone (INN, USAN, BAN), also known as Carpiperone and Floropipamide or Fluoropipamide, and as Floropipamide hydrochloride (JAN), is a typical antipsychotic of the butyrophenone family used in the treatment of schizophrenia. It is or has been marketed under brand names including Dipiperon, Dipiperal, Piperonil, Piperonyl, and Propitan. Pipamperone acts as an antagonist of the 5-HT2A, 5-HT2B, 5-HT2C D2, D3, D4, α1-adrenergic, and α2-adrenergic receptors. It shows the much higher affinity for the 5-HT2A and D4 receptors over the D2receptor (15-fold in the case of the D4 receptor, and even higher in the case of the 5-HT2A receptor), is regarded as "highly selective" for the former two sites at low doses. Pipamperone has low and likely insignificant affinity for the H1 and mACh receptors, as well as for other serotonin and dopamine receptors. Low-dose pipamperone (5 mg twice daily) has been found to accelerate and enhance the antidepressant effect of citalopram. Pipamperone is approved in some European countries. At its usually recommended antipsychotic dose (120–360 mg/d), it has relatively weak neuroleptic activity because it is only moderately effective as a dopamine D2-receptor antagonist, even at high doses.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11672571	Antagonist 2849	7.0 nM [Ki]
Serotonin 2c (5-HT2c) receptor 131 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11672571	Antagonist 2849	54.0 nM [Ki]
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8935801	Antagonist 2849	93.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Major depressive disorder 179 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21349239	Primary		Phase II 1147	Dipiperon Approved Use Indication: Short-term treatment of states of agitation and aggression during acute and chronic psychotic states (schizophrenia, chronic non-schizophrenic delirium: paranoid delusions, chronic hallucinatory psychoses).
Schizophrenia 305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24614672	Primary		Approved 8583	Dipiperon Approved Use Indication: Short-term treatment of states of agitation and aggression during acute and chronic psychotic states (schizophrenia, chronic non-schizophrenic delirium: paranoid delusions, chronic hallucinatory psychoses).

C_max

Value	Dose	Co-administered	Analyte	Population
266 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12109042/	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		PIPAMPERONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3107 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12109042/	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:		PIPAMPERONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2400 mg single, oral Lethal dose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/30761754/	unhealthy, ADOLESCENT\|ADULT Health Status: unhealthy Age Group: ADOLESCENT\|ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30761754/	Other AEs: Death... Other AEs: Death (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/30761754/
638 mg single, oral Overdose Dose: 638 mg Route: oral Route: single Dose: 638 mg Sources: https://www.clinicaltherapeutics.com/article/S0149-2918(13)00655-3/fulltext	unknown, ADOLESCENT\|ADULT Health Status: unknown Age Group: ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.clinicaltherapeutics.com/article/S0149-2918(13)00655-3/fulltext	Other AEs: Somnolence, Coma... Other AEs: Somnolence (grade 1, 43%) Coma (grade 2-3, 7%) Dystonic reactio (grade 1-2, 9%) Seizures (grade 2, 2%) Disorientatio (grade 2, 2%) Agitation mental (grade 1-2, 4%) Tachycardia (grade 1, 13%) Hypotension (grade 1-2, 13%) Electrocardiogram QTc interval prolonged (grade 1-2, 20%) AV block (grade 2, 2%) Xerostomia (grade 1, 7%) Gastrointestinal symptom NOS (grade 1, 7%) Urinary retention (grade 2, 2%) Sources: https://www.clinicaltherapeutics.com/article/S0149-2918(13)00655-3/fulltext
4000 mg single, oral Lethal dose Dose: 4000 mg Route: oral Route: single Dose: 4000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/30761754/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30761754/	Other AEs: Death... Other AEs: Death (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/30761754/
80 mg 2 times / day multiple, oral Recommended Dose: 80 mg, 2 times / day Route: oral Route: multiple Dose: 80 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27111131/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27111131/	Disc. AE: Hypothermia... AEs leading to discontinuation/dose reduction: Hypothermia Sources: https://pubmed.ncbi.nlm.nih.gov/27111131/

AEs

PubMed

Title	Date	PubMed
Identification and quantification of 30 antipsychotics in blood using LC-MS/MS.	2010-08	20648676
A field study on 8 pharmaceuticals and 1 pesticide in Belgium: removal rates in waste water treatment plants and occurrence in surface water.	2010-07-15	20471061
Analysis of risperidone and its metabolite in plasma and saliva by LC with coulometric detection and a novel MEPS procedure.	2010-06-15	20441937
Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia.	2010-03	19856012
Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with major depressive disorder--the EMC trial.	2010-02-26	20187947
Clinical trials in CNS--SMi's eighth annual conference.	2010-02	20127552
Beyond the dopamine receptor: novel therapeutic targets for treating schizophrenia.	2010	20954431
Increased D-amino acid oxidase expression in the bilateral hippocampal CA4 of schizophrenic patients: a post-mortem study.	2009-12	19823762
Drugs associated with more suicidal ideations are also associated with more suicide attempts.	2009-10-02	19798416
Antipsychotic use and the risk of hip/femur fracture: a population-based case-control study.	2009-09	19156348
Antipsychotics and risk of venous thromboembolism: A population-based case-control study.	2009-08-09	20865083
The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913).	2008-12-22	19102734
Evaluation of serotonin-2A receptor occupancy with 123I-5-I-R91150 and single-photon emission tomography before and after low-dose pipamperone administration in the canine brain.	2008-08	18753826
Comparison of matrix effects in HPLC-MS/MS and UPLC-MS/MS analysis of nine basic pharmaceuticals in surface waters.	2008-05	18343682
[Recurrent dysregulation of body temperature during antipsychotic pharmacotherapy].	2008-03	17902059
Validation of a solid-phase extraction and liquid chromatography-electrospray tandem mass spectrometric method for the determination of nine basic pharmaceuticals in wastewater and surface water samples.	2008-02-29	18237738
[Pipamperone and the treatment of impulsive aggressive behaviour].	2008	18324605
[Enuresis in therapy with psychotropic drugs].	2007-09-05	17894120
Hypothermia following antipsychotic drug use.	2007-06	17401555
Forty years of antipsychotic Drug research--from haloperidol to paliperidone--with Dr. Paul Janssen.	2007	18074755
Influence of the antipsychotic drug pipamperone on the expression of the dopamine D4 receptor.	2006-12-03	16978659
Management of a severe forceful breather with Rett syndrome using carbogen.	2006-11	16765005
Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach.	2006-10-20	16798119
Tackling matrix effects during development of a liquid chromatographic-electrospray ionisation tandem mass spectrometric analysis of nine basic pharmaceuticals in aqueous environmental samples.	2006-08-04	16720025
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].	2006-06	16856516
Stability indicating LC method for the determination of pipamperone.	2005-10-04	16040223
Unbiased descriptor and parameter selection confirms the potential of proteochemometric modelling.	2005-03-10	15760465
In-patient psychiatric-psychotherapeutic treatment of mothers with a generalized anxiety disorder--does the co-admission of their children influence the treatment results? A prospective, controlled study.	2004-11-30	15628646
Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in serum with liquid chromatography-electrospray ionization mass spectrometry.	2003-12	14708881
Quantitative determination of piritramide in human serum applying liquid chromatography-two-stage mass spectrometry.	2003-01-05	12450524
Differential-pulse polarography determination of pipamperone in pharmaceutical formulations.	2002-11-07	12408934
Role of 5-HT(2) receptors in the tryptamine-induced 5-HT syndrome in rats.	2002-07	12218512
Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by HPLC and fluorescence detection following LSD ImmunElute extraction.	2002-04	11991536
[Models of drug treatment in the attention deficit disorder with hyperactivity].	2002-02	12447798
Atypical kinetics for a series of putative dopamine antagonists to reverse the low-magnitude Ca2+ phase in the dopamine-bound D2short receptor state.	2002-01	11862337
Pharmacokinetics of pipamperone from three different tablet formulations.	2002	12109042
Different regulation of rat 5-HT(2A) and rat 5-HT(2C) receptors in NIH 3T3 cells upon exposure to 5-HT and pipamperone.	2001-08-03	11672571
Antipsychotic-induced extrapyramidal syndromes. Risperidone compared with low- and high-potency conventional antipsychotic drugs.	2001-07	11549212
Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome.	2001-01-26	11164765
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.	1996-03	8935801

Patents

Sample Use Guides

In Vivo Use Guide

Initial Dose 20 mg (1/2 tablet), Average dosage 40-120 mg (1-3 tablets)

Route of Administration: Oral

In Vitro Use Guide

NIH 3T3 cell lines were cultured in Dulbecco’s modified Eagle medium with 10% heat-inactivated dialysed calf serum (30 min at 56 OC; 5-HT concentration 8 nM.) supplemented with the agonist 5-HT (10 mkM) or the antagonist pipamperone (10 mkM) for 15 min or 48 h. Untreated cells were grown in parallel. Cells were grown on 150 mm petri dishes at 37 OC in a humidified atmosphere containing 5% CO2.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:17:27 GMT 2025` Edited by `admin` on `Mon Mar 31 19:17:27 GMT 2025`
Record UNII	IT085U64JB
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIPAMPERONE DIHYDROCHLORIDE

Preferred Name

English

PIPAMPERONE HYDROCHLORIDE

Common Name

English

PIPAMPERONE 2HCL

Common Name

English

NSC-170981

Code

English

PIPAMPERONE HYDROCHLORIDE [JAN]

Common Name

English

DIPIPERON

Brand Name

English

Pipamperone hydrochloride [WHO-DD]

Common Name

English

PIPAMPERONE DIHYDROCHLORIDE [MI]

Common Name

English

1'-(3-(P-FLUOROBENZOYL)PROPYL)-(1,4'-BIPIPERIDINE)-4'-CARBOXAMIDE DIHYDROCHLORIDE

Common Name

English

PIPAMPERONE HYDROCHLORIDE [MART.]

Common Name

English

Code System Code Type Description

SMS_ID

100000085607