Page last updated: 2024-11-04

pipamperone

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Pipamperone is a butyrophenone derivative with antipsychotic properties. It was synthesized in the 1960s and was initially investigated as a potential treatment for schizophrenia. Pipamperone has a complex mechanism of action, which involves blocking dopamine receptors in the brain, particularly D2 receptors. It also exhibits some affinity for serotonin receptors, which may contribute to its therapeutic effects. Research has explored its use in treating conditions like schizophrenia, anxiety, and Tourette syndrome. However, its use has been limited due to potential side effects, including extrapyramidal symptoms and metabolic disturbances. Further research is ongoing to understand its therapeutic potential and address its limitations.'
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pipamperone: RN given refers to parent cpd; structure [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

pipamperone : A member of the class of bipiperidines that is 1,4'-bipiperidine which is substituted at the 1' and 4' positions by 4-(p-fluorophenyl)-4-oxobutyl and carboxamide groups, respectively. A first generation antipsychotic, its properties are generally similar to those of haloperidol. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID4830
CHEMBL ID440294
CHEBI ID78549
SCHEMBL ID2412
MeSH IDM0047214

Synonyms (85)

Synonym
nsc 759178
pipamperonum
1,4'-bipiperidine)-4'-carboxamide, 1'-(4-(4-fluorophenyl)-4-oxobutyl)-
5-22-13-00536 (beilstein handbook reference)
pipamperona
unii-5402501f0w
5402501f0w ,
gtpl92
1893-33-0
D02622
floropipamide
pipamperone (usan/inn)
mcn-jr-3345
isonipacotamide, 1-(3-(p-fluorobenzoyl)propyl)-4-piperidino-
dipiperal
piperonyl
dipiperone
4'-fluoro-4-(4-n-piperidino-4-carbamidopiperidino)butyrophenone
1'-(3-(p-fluorobenzoyl)propyl)-(1,4'-bipiperidine)-4'-carboxamide
r 3345
pipamperona [inn-spanish]
(1,4'-bipiperidine)-4'-carboxamide, 1'-(4-(4-fluorophenyl)-4-oxobutyl)-
p-fluoro-gamma-(4-piperidino-4-carbamoylpiperidino)butyrophenone
ccris 9071
brn 0496532
pipamperone [usan:inn:ban]
pipamperonum [inn-latin]
PDSP1_001560
pipamperone
(1,4'-bipiperidine)-4'-carboxamide, 1'-(3-(p-fluorobenzoyl)propyl)-
PDSP2_001544
NCGC00165864-01
pipaneperone
CHEMBL440294
r-3345
chebi:78549 ,
nsc-759178
L000727
1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidin-1-ylpiperidine-4-carboxamide
bdbm81483
nsc_4830
cas_1893-33-0
HMS3264G14
nsc759178
pharmakon1600-01505690
pipamperone [mart.]
pipamperone [who-dd]
pipamperone [usan]
pipamperone [mi]
pipamperone [inn]
1'-[4-(4-fluorophenyl)-4-oxobutyl]-1,4'-bipiperidine-4'-carboxamide
BRD-K26801045-001-01-1
CCG-213514
SCHEMBL2412
1-(4-fluorophenyl)-4-(4-piperidino-4-carbamoylpiperidino)-1-butanone
DTXSID8048369
propitan (salt/mix)
1'-(3-(p-fluorobenzoyl)propyl)(1,4'-bipiperidine)-4'-carboxamide
isonipecotamide, 1-(3-(p-fluorobenzoyl)propyl)-4-piperidino-
p-fluoro-.gamma.-(4-piperidino-4-carbamoylpiperidino)butyrophenone
[1,4'-bipiperidine]-4'-carboxamide, 1'-[4-(4-fluorophenyl)-4-oxobutyl]-
AC-32938
AB01563106_01
DB09286
1'-(4-(4-fluorophenyl)-4-oxobutyl)-1,4'-bipiperidine-4'-carboxamide
SR-05000001930-1
sr-05000001930
pipamperone dihydrochloride approx. 99
pipamperon
SBI-0206899.P001
Q415118
pipamperone free base
1'-(4-(4-fluorophenyl)-4-oxobutyl)-[1,4'-bipiperidine]-4'-carboxamide
1893-33-0 (free base)
pipamperonedihydrochlorideapprox.99
mfcd00242979
1'-[4-(4-fluorophenyl)-4-oxobutyl]-[1,4'-bipiperidine]-4'-carboxamide
P2315
HY-100703
mcn-jr 3345
CS-0020023
floropipamide; mcn-jr 3345; r 3345
A929272
MS-26084
AKOS040734867

Research Excerpts

Overview

Pipamperone is a frequently prescribed antipsychotic in the Netherlands, Belgium, and Germany. It acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses.

ExcerptReferenceRelevance
"Pipamperone is a frequently prescribed antipsychotic in children and adolescents in the Netherlands, Belgium, and Germany. "( Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents.
Bahmany, S; de Winter, BCM; Dieleman, GC; Dierckx, B; Egberts, KM; Gerlach, M; Hillegers, MHJ; Kloosterboer, SM; Koch, BCP; Kouijzer, MEJ; Reichart, CG; van Daalen, E; van Gelder, T, 2020
)
3.44
"Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses."( 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.
Buntinx, E; Crawford, GM; Haazen, L; McConnachie, A; Nemeroff, CB; Schatzberg, AF; Schlaepfer, T; Wade, AG, 2011
)
1.39

Treatment

ExcerptReferenceRelevance
"Pipamperone treatment was considered superior to previous medication in 13 out of 15 patients who had previously been receiving other drugs."( Treating severe maladjustment with pipamperone (Dipiperon).
Noordhuizen, GJ,
)
1.13

Pharmacokinetics

ExcerptReferenceRelevance
" The geometric mean Cmax of pipamperone for both the reference product and test product A was 266 ng/ml and for test product B 263 ng/ml."( Pharmacokinetics of pipamperone from three different tablet formulations.
Groenewoud, G; Hundt, HK; Jordaan, PJ; Kummer, M; Potgieter, GE; Schall, R; Sewarte-Ross, G, 2002
)
0.93

Compound-Compound Interactions

ExcerptReferenceRelevance
" Physicians and pharmacists should be cautious for drug-drug interactions when pipamperon is prescribed, especially in combination with other QT-prolongating agents."( Drug-drug interaction related to the use of pipamperon and ondansetron in a child treated for leukemia.
Bauters, T; Bordon, V; Buts, S; Laureys, G, 2018
)
0.48

Dosage Studied

Pipamperone drops were delivered in a plastic squeeze bottle (LDPE bottle), which makes correct dosing almost impossible. Initial dosage was 40 mg b.

ExcerptRelevanceReference
" Each consecutive dosing was separated by a washout period of 14 days."( Pharmacokinetics of pipamperone from three different tablet formulations.
Groenewoud, G; Hundt, HK; Jordaan, PJ; Kummer, M; Potgieter, GE; Schall, R; Sewarte-Ross, G, 2002
)
0.64
"Medication is not always delivered in a safe dosing format."( [Overdosing of pipamperone from a squeeze bottle].
Bosch, TM; de Roo, JHC; Del Canho, R; van Rhijn, A,
)
0.48
" The pipamperone drops were delivered in a plastic squeeze bottle (LDPE bottle), which makes correct dosing almost impossible."( [Overdosing of pipamperone from a squeeze bottle].
Bosch, TM; de Roo, JHC; Del Canho, R; van Rhijn, A,
)
1
" Currently, divergent pediatric dosing recommendations exist."( Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents.
Bahmany, S; de Winter, BCM; Dieleman, GC; Dierckx, B; Egberts, KM; Gerlach, M; Hillegers, MHJ; Kloosterboer, SM; Koch, BCP; Kouijzer, MEJ; Reichart, CG; van Daalen, E; van Gelder, T, 2020
)
2
"6-mg/kg dosage was better than a fixed dosage to attain the concentration range observed in responders."( Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents.
Bahmany, S; de Winter, BCM; Dieleman, GC; Dierckx, B; Egberts, KM; Gerlach, M; Hillegers, MHJ; Kloosterboer, SM; Koch, BCP; Kouijzer, MEJ; Reichart, CG; van Daalen, E; van Gelder, T, 2020
)
2
" When dosing pipamperone in children and adolescents, bodyweight should be taken into account."( Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents.
Bahmany, S; de Winter, BCM; Dieleman, GC; Dierckx, B; Egberts, KM; Gerlach, M; Hillegers, MHJ; Kloosterboer, SM; Koch, BCP; Kouijzer, MEJ; Reichart, CG; van Daalen, E; van Gelder, T, 2020
)
2.37
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
first generation antipsychoticAntipsychotic drugs which can have different modes of action but which tend to be more likely than second generation antipsychotics to cause extrapyramidal motor control disabilities such as body rigidity or Parkinson's disease-type movements; such body movements can become permanent even after treatment has ceased.
serotonergic antagonistDrugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonergic agonists.
dopaminergic antagonistA drug that binds to but does not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (5)

ClassDescription
monocarboxylic acid amideA carboxamide derived from a monocarboxylic acid.
aromatic ketoneA ketone in which the carbonyl group is attached to an aromatic ring.
organofluorine compoundAn organofluorine compound is a compound containing at least one carbon-fluorine bond.
bipiperidines
tertiary amino compoundA compound formally derived from ammonia by replacing three hydrogen atoms by organyl groups.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (1)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency0.15850.003245.467312,589.2998AID2517
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (17)

Assay IDTitleYearJournalArticle
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID624223Antagonists at Human 5-Hydroxytryptamine receptor 5-HT2A1996Psychopharmacology, Mar, Volume: 124, Issue:1-2
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
AID624231Antagonists at Human 5-Hydroxytryptamine receptor 5-HT1D1996Psychopharmacology, Mar, Volume: 124, Issue:1-2
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
AID1346264Human 5-HT1B receptor (5-Hydroxytryptamine receptors)1996Psychopharmacology, Mar, Volume: 124, Issue:1-2
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
AID624215Antagonists at Human 5-Hydroxytryptamine receptor 5-HT1A1996Psychopharmacology, Mar, Volume: 124, Issue:1-2
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
AID1346528Human 5-HT1D receptor (5-Hydroxytryptamine receptors)1996Psychopharmacology, Mar, Volume: 124, Issue:1-2
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
AID1259419Human 5-HT2A receptor (5-Hydroxytryptamine receptors)1996Psychopharmacology, Mar, Volume: 124, Issue:1-2
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
AID1345615Human 5-HT1A receptor (5-Hydroxytryptamine receptors)1996Psychopharmacology, Mar, Volume: 124, Issue:1-2
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
AID1346037Human H1 receptor (Histamine receptors)1996Psychopharmacology, Mar, Volume: 124, Issue:1-2
Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding.
AID196752Compound was evaluated for its activity at membrane-bound receptor (M+L+P fraction) from rat frontal cortex1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
In vitro labeling of serotonin-S2 receptors: synthesis and binding characteristics of [3H]-7-aminoketanserin.
AID311934Dissociation constant, pKa of the compound2008Journal of medicinal chemistry, Jan-24, Volume: 51, Issue:2
Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model.
AID196754Compound was evaluated for its activity at membrane-bound receptor (M+L+P fraction) from rat frontal cortex1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
In vitro labeling of serotonin-S2 receptors: synthesis and binding characteristics of [3H]-7-aminoketanserin.
AID196755Compound was evaluated for its activity at solubilized receptor (CHAPS/salt-solubilized preparation) from rat frontal cortex1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
In vitro labeling of serotonin-S2 receptors: synthesis and binding characteristics of [3H]-7-aminoketanserin.
AID196753Compound was evaluated for its activity at solubilized receptor (CHAPS/salt-solubilized preparation) from rat frontal cortex1986Journal of medicinal chemistry, Sep, Volume: 29, Issue:9
In vitro labeling of serotonin-S2 receptors: synthesis and binding characteristics of [3H]-7-aminoketanserin.
AID311933Inhibition of ASM in rat PC12 cells assessed as residual activity at 10 uM2008Journal of medicinal chemistry, Jan-24, Volume: 51, Issue:2
Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model.
AID227718Binding energy by using the equation deltaG obsd = -RT ln KD1984Journal of medicinal chemistry, Dec, Volume: 27, Issue:12
Functional group contributions to drug-receptor interactions.
AID311935Partition coefficient, log P of the compound2008Journal of medicinal chemistry, Jan-24, Volume: 51, Issue:2
Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (67)

TimeframeStudies, This Drug (%)All Drugs %
pre-199028 (41.79)18.7374
1990's8 (11.94)18.2507
2000's13 (19.40)29.6817
2010's17 (25.37)24.3611
2020's1 (1.49)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 84.20

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index84.20 (24.57)
Research Supply Index4.44 (2.92)
Research Growth Index4.55 (4.65)
Search Engine Demand Index145.98 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (84.20)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials8 (10.53%)5.53%
Reviews1 (1.32%)6.00%
Case Studies19 (25.00%)4.05%
Observational0 (0.00%)0.25%
Other48 (63.16%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (4)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Phase IIa Proof of Concept Study of Pipamperone/Citalopram (PipCit) Versus Citalopram in the Treatment of Major Depressive Disorder (MDD) [NCT00672659]Phase 2165 participants (Actual)Interventional2008-02-29Completed
Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in the Treatment of Moderate to Severe Major Depressive Disorder (MDD): a Randomized, Double-blind Phase III Study of 10 Weeks [NCT01312922]Phase 3555 participants (Actual)Interventional2011-09-30Completed
POC Study of Pipamperone 15mg Added to Stable Risperidone or Paliperidone Treatment in Chronic Schizophrenic and Schizoaffective Patients With Residual Symptoms: a Phase I/IIa, Randomized, Double-blind, Placebo-controlled Trial of 7 Weeks [NCT01450514]Phase 27 participants (Actual)Interventional2012-03-31Completed
Pharmacovigilance in Gerontopsychiatric Patients [NCT02374567]Phase 3407 participants (Actual)Interventional2015-01-31Terminated
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT01312922 (1) [back to overview]Early and Sustained (Antidepressant) Response (ESR) Rate

Early and Sustained (Antidepressant) Response (ESR) Rate

Early and Sustained Response (ESR) is defined as a MADRS total score reduction from Baseline of 50% or more and a MADRS total score ≤16 at Week 2, Week 3, Week 4, and Week 6. (NCT01312922)
Timeframe: From (end of) Week 2 visit to (end of) Week 6 visit

InterventionParticipants (Count of Participants)
PNB0117
Citalopram17
Pipamperone17

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