Benperidol
Benperidol, sold under the trade name Anquil among others, is a typical antipsychotic primarily used to treat hypersexuality syndromes and can be used to treat schizophrenia. It is a highly potent butyrophenone derivative and is the most potent neuroleptic in the European market, with chlorpromazine equivalency as high as 75 to 100. It is sometimes prescribed to sex offenders as a condition of their parole, as an alternative to anti-androgen drugs such as cyproterone acetate.
Benperidol was discovered by Janssen Pharmaceutica in 1961 and has been marketed since 1966. It is mainly used in Germany, but it is also available in Belgium, Greece, the Netherlands, and the United Kingdom.
Pharmacology
Pharmacodynamics
Benperidol is a strong dopamine receptor antagonist and D4 ) with weaker serotonin receptor antagonism. In high doses, it has antihistaminergic and alpha-adrenergic properties. It possesses minimal anticholinergic properties.| Site | Ki | Action | Ref |
| 5-HT2A | 3.75 | Antagonist | |
| D1 | 4,100 | Antagonist | |
| D2 | 0.027 | Antagonist | |
| D4 | 0.06 | Antagonist |
Although benperidol was developed relatively early in the history of antipsychotic drugs, it exhibits a uniquely high and selective affinity for the human dopamine D2 receptor when compared with all other human dopamine receptor subtypes. This is evident from its nanomolar binding affinities, which stand out even among both typical and atypical antipsychotics. Benperidol is also considered to possess one of the greatest selectivity ratios for dopamine receptors over 5-HT2A serotonin receptors, although this distinction is surpassed by certain neuroleptics such as amisulpride and sulpiride. Dopamine receptors play central roles not only in cognition, emotion, and motor control—key domains affected in schizophrenia—but also in various unconscious biological processes. The emphasis on D2 receptor blockade in antipsychotic drug design stems from its critical role in these functions and its dense expression in brain regions implicated in schizophrenia, such as the striatum and frontal cortex. Benperidol's preferential binding to the D2 receptor—over other dopamine receptor subtypes such as D3 and D4—is also unusually strong, with approximately a twofold greater selectivity. This distinguishes it from antipsychotics like haloperidol and perphenazine, which show more balanced D2/D3 binding ratios, as well as from cariprazine, which demonstrates an even higher D3 affinity relative to D2.