Absorption, Distribution and Excretion
Mainly via the kidneys

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Metabolism / Metabolites
Pipamperone is metabolised in the liver.

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Biological Half-Life
17-26h

Pipamperone is 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. It has a role as a first generation antipsychotic, a serotonergic antagonist and a dopaminergic antagonist. It is a monocarboxylic acid amide, an aromatic ketone, an organofluorine compound, a member of bipiperidines and a tertiary amino compound. It is a conjugate base of a pipamperone(2+).
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. 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.
See also: Pipamperone dihydrochloride (annotation moved to).

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Drug Indication
Treatment of chronic psychoses and states of aggressiveness of various origins.

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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. This drug is a selective 5-HT2A, D1 and D4 antagonist. Extrapyramidal adverse effects also appear to be limited in pipamperone treatment compared to traditional antipsychotic medications due to its high receptor selectivity. 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.

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Pharmacodynamics
Pipamperone is an antipsychotic medication that has sedative effects, which may be beneficial in the management of agitation and disordered sleep. 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. 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.

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.)