Dopamine D2 Receptor: Benperidol is a butyrophenone derivative and a specific dopamine antagonist, selective for the D2 receptor. It has the highest neuroleptic potency in terms of D2 receptor blockade. No specific IC50/Ki values are provided in this document. [1]
Serotonin Receptors: Benperidol also binds to serotonin receptors, but to a lesser extent than dopamine receptors. [1]
Other Targets: At high doses, benperidol has antihistaminergic and alpha-adrenergic properties. Its anticholinergic effects are small. [1]

Clinical Efficacy (vs. Perphenazine): In one unpublished, poorly reported randomized controlled trial (N=40, duration 30 days), oral benperidol (6-12 mg/day) was compared with oral perphenazine (12-24 mg/day). At the end of the trial, raters judged the global effect of treatment. People allocated to benperidol were more likely to be "no better or worse" than those given perphenazine (1 RCT, n=40, RR 8.00 CI 2.1 to 30, NNH 1.4 CI 1 to 2). This suggests benperidol was inferior to perphenazine in this single small study, but the results should be viewed with great caution due to poor methodology. [1]
Leaving the Study Early: No person left the study before completion (30 days) in the Eckmann 1984 trial. [1]
Lack of Placebo-Controlled Trials: The search did not identify any placebo-controlled trials of benperidol. [1]

Absorption: Benperidol is absorbed easily. [1]
First-Pass Effect: It has a high first-pass effect. [1]
Excretion: Only one percent of the original benperidol can be found in the urine. [1]
Metabolites: Little is known about the metabolites of this compound. [1]
Half-Life: Benperidol has a short half-life of approximately 8 hours. [1]
Dosing Frequency: Due to its short half-life, benperidol should be administered three times per day. [1]
Recommended Dose: The recommended initial dose is 2 to 6 mg/day; the maximum dose is 40 mg/day. [1]
Routes of Administration: Benperidol is usually taken orally but can also be given by intramuscular injection for rapid treatment of acutely disturbed psychotic patients. [1]

Extrapyramidal Side Effects: Benperidol has been associated with a high risk of adverse effects such as rigidity, mask-like appearance, tremor, stooped shuffling gait, and other extrapyramidal effects including akathisia (inner feeling of restlessness), acute dystonias (acute spinal and ocular rigidity), and tardive dyskinesia (slow onset of repetitive movements of the face and body). This high risk is attributed to its high potency in D2 receptor blockade. [1]
No Adverse Event Data in Included Trial: The single included trial (Eckmann 1984) did not report usable data on adverse effects. [1]

[1]. Benperidol for schizophrenia. Cochrane Database Syst Rev. 2005;2005(2):CD003083.

3-[1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidinyl]-1H-benzimidazole-2-one is an aromatic ketone. Benzimidazole has been used in clinical trials for the treatment of dementia, depression, schizophrenia, anxiety disorders, and psychosomatic illnesses. It is a butyrylbenzene compound with general properties similar to fluperidazole. It has been used to treat sexual dysfunction. (Excerpt from Martindale Pharmacopoeia, 30th edition, page 567)

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Background: Benperidol is a relatively old antipsychotic drug formulated in the 1960s and marketed since 1966. It is a butyrophenone derivative and a specific dopamine antagonist. It has been used in Germany for over 30 years and is also available in Belgium, Greece, Italy, the Netherlands, and the UK. In the UK, it is also used as a sexual suppressant. [1]
Mechanism of Action: Benperidol exerts its antipsychotic effects primarily through potent and selective antagonism of dopamine D2 receptors. Its potency in terms of dopamine receptor antagonism is estimated to be 100 times higher than that of chlorpromazine, and haloperidol is supposed to reach only 60% of benperidol's potency. [1]
Unusual Profile: Benperidol's unusual receptor binding profile (high D2 potency with lesser effects on other receptors) may render it valuable for certain subgroups of people with schizophrenia, such as those with treatment-resistant illness. [1]
Lack of Evidence: Despite being used for decades, there are insufficient data from randomized trials to assess the clinical effects of benperidol. Only one unpublished, poorly reported RCT was identified comparing it to perphenazine. No placebo-controlled trials exist. [1]
Clinical Implications: The lack of evidence means that possible benefits and harms of prescribing benperidol must be weighed against alternative, better-researched treatments. Patients should be informed about this lack of data. [1]
Research Implications: Well-designed, conducted, and reported randomized controlled trials of benperidol are urgently needed, particularly given its interesting receptor binding profile and potential value for treatment-resistant patients. [1]

C22H24FN3O2

381.4514

381.185

2062-84-2

Benperidol-d4

16363

White to off-white solid powder

1.2±0.1 g/cm3

7.96E-17mmHg at 25°C

1.595

4.09

1

4

6

28

556

0

C1=CC=C2C(=C1)N=C(N2C3CCN(CCCC(=O)C4=CC=C(C=C4)F)CC3)O

FEBOTPHFXYHVPL-UHFFFAOYSA-N

InChI=1S/C22H24FN3O2/c23-17-9-7-16(8-10-17)21(27)6-3-13-25-14-11-18(12-15-25)26-20-5-2-1-4-19(20)24-22(26)28/h1-2,4-5,7-10,18H,3,6,11-15H2,(H,24,28)

3-[1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl]-1H-benzimidazol-2-one

Anquil McN-JR-4584Benperidol R 4584 R4584R-4584 McN JR 4584 McNJR4584

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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 (~262.16 mM)

Solubility in Formulation 1: ≥ 1.67 mg/mL (4.38 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 16.7 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: ≥ 1.67 mg/mL (4.38 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 16.7 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.)