Pipamperone targets multiple receptors, including serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, dopamine D2, D3, and D4 receptors, and α1- and α2-adrenergic receptors. It acts as an antagonist at these receptors. Its blockade of serotonin 5-HT2A and α1 receptors is particularly notable. This broad receptor profile contributes to its antipsychotic and sedative effects. Its selectivity profile supports its therapeutic role in modulating serotonergic and dopaminergic neurotransmission.

In vitro, pipamperone binds to and antagonizes serotonin, dopamine, and adrenergic receptors. Its activity is assessed using radioligand binding assays and functional assays. The compound's affinity for various receptors is characterized by its Ki values. Its ability to block receptor-mediated signaling is assessed in cell-based assays. Specific IC50 and Ki values are not detailed in the provided search results.

In vivo, pipamperone is used as an antipsychotic for the treatment of chronic psychoses and states of aggressiveness. It has sedative and antipsychotic properties. It is prescribed to prevent impulsive aggressive behavior in patients with intermittent explosive disorder, personality disorders, or mental retardation. Its effects are mediated through its broad receptor antagonism.

The in vitro activity of pipamperone is assessed using radioligand binding assays and functional assays. For receptor binding, membrane preparations from cells expressing specific receptors are incubated with radiolabeled ligands in the presence of varying concentrations of pipamperone. The displacement of the radiolabeled ligand is measured to determine the Ki. For functional assays, cells expressing specific receptors are treated with pipamperone and stimulated with receptor agonists.

For cellular assays, cells expressing specific receptors (e.g., 5-HT2A, D2) are cultured in appropriate media. Cells are treated with various concentrations of pipamperone (typically 0.1 nM to 10 µM) for defined periods. Receptor-mediated signaling (e.g., calcium mobilization, cAMP accumulation) is measured. Cell viability is assessed using standard assays.

In vivo, pipamperone is typically administered orally to patients. Dosing regimens vary depending on the indication and patient response. Efficacy is assessed by measuring changes in psychiatric rating scales and behavioral assessments. In animal models, the compound is administered at various doses, and its effects on behavior (e.g., locomotor activity, aggression) are assessed.

Absorption, Distribution and Excretion
Primarily excreted via the kidneys. Metabolism/Metabolites Piperazine is metabolized in the liver. Biological Half-Life 17-26 hours
Pipamperone free base has a molecular weight of 375.49 g/mol and a molecular formula of C21H30FN3O2. It is a monocarboxylic acid amide, an aromatic ketone, an organofluorine compound, a member of bipiperidines, and a tertiary amino compound. The compound should be stored under appropriate conditions as recommended by the manufacturer. Specific solubility and pharmacokinetic parameters are not detailed in the provided search results.

Pipamperone can cause side effects including sedation, extrapyramidal symptoms, and anticholinergic effects. The compound is intended for therapeutic use under appropriate medical supervision. Comprehensive toxicological studies are required to establish its full safety profile. Standard laboratory safety precautions should be followed when handling the compound. Pipamperone is not approved for all indications in all regions.

Pipamperone belongs to the bipiperidine class of compounds, with the structure 1,4'-bipiperidine, substituted at the 1' and 4' positions by 4-(p-fluorophenyl)-4-oxobutyl and carboxamide groups, respectively. As a first-generation antipsychotic, its properties are similar to haloperidol. It functions as a first-generation antipsychotic, a serotonergic antagonist, and a dopaminergic antagonist. Pipamperone is a monocarboxylic acid amide, aromatic ketone, organofluorine compound, bipiperidine compound, and tertiary amine compound. It is the conjugate base of piperone (2+). Pipamperone is a typical representative of butyrophenone antipsychotics used to treat schizophrenia. It was developed by Janssen Pharmaceuticals in 1961, and the first round of clinical trials began in 1963. To improve the pharmacological effects of haloperidol, Janssen discovered that piperone possessed significant antitryptamine activity, and its pharmacological properties were unlike those of haloperidol and all other known antipsychotics at the time. Some studies suggest that piperacillin was the first atypical antipsychotic. Interestingly, when risperidone was introduced, Janssen Pharmaceuticals stated that it was a potent version of piperacillin. Risperidone, synthesized in 1984, has similar pharmacological properties to methylphenidate; both block serotonin more effectively than dopamine.
See also: Methylphenidate dihydrochloride (note moved to).
Indications
Treatment of chronic psychosis and aggressive states of various causes.
Mechanism of Action
Methylphenidate primarily binds to 5-HT2A receptors, has almost identical affinity for D4 receptors, and moderate affinity for 5-HT2C, D2, D3, 1-, and 2β-adrenergic receptors. It is a selective 5-HT2A, D1, and D4 receptor antagonist. Due to its high receptor selectivity, methylphenidate treatment results in fewer extrapyramidal adverse reactions compared to conventional antipsychotics. Pipamperone has a 15-fold higher affinity for the D4 receptor than for the D2 receptor. Studies have shown that the D4 receptor may play a role in dopamine regulation of GABAergic neuronal activity. Pipamperone is an antipsychotic drug with sedative effects and may help treat agitation and sleep disorders. Pipamperone possesses anti-dopaminergic and anti-serotonergic properties, and its anti-aggro properties and ability to regulate sleep rhythms in patients with mental illness have been demonstrated. One study showed that Pipamperone can increase the expression of the D4 (dopaminergic) receptor, which explains why it helps alleviate positive psychotic symptoms such as delusions and hallucinations.
Pipamperone is a typical antipsychotic of the butyrophenone family. It is an antagonist of multiple serotonin, dopamine, and adrenergic receptors. Pipamperone is used in the treatment of chronic psychoses and states of aggressiveness. It has sedative and antipsychotic properties. Pipamperone is available for therapeutic use under appropriate regulatory oversight in some regions.

C21H30FN3O2

375.4802

375.232

1893-33-0

1893-33-0;2448-68-2 (HCl);

4830

White to off-white solid powder

1.174g/cm3

563.7ºC at 760 mmHg

126°C(lit.)

294.7ºC

9.88E-13mmHg at 25°C

1.556

3.17

1

5

7

27

506

0

FC1C([H])=C([H])C(=C([H])C=1[H])C(C([H])([H])C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C(C(N([H])[H])=O)(C([H])([H])C1([H])[H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])=O

AXKPFOAXAHJUAG-UHFFFAOYSA-N

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)

1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidin-1-ylpiperidine-4-carboxamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~266.33 mM)
0.1 M HCL : 25 mg/mL (~66.58 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)