Пимозид

Описание

Pimozide is a dopamine receptor antagonist (Kis = 2.4, 0.3, and 1.8 nM for D2, D3, and D4 receptors, respectively). It also binds to eight additional receptors (Kds = 25-3,100 nM for the human receptors) and inhibits the voltage-gated sodium channel Nav1.2 and the voltage-gated potassium channel Kv11.1 (IC50s = 42 and 340 nM, respectively). Pimozide (0.5, 1, and 2 mg/kg) decreases the number of licks and reduces fluid intake of a sweetened solution in rats. It decreases the number of threats and attacks and increases immobility time in the neutral arena aggression test, indicating increased passiveness, in male mice when administered at a dose of 0.75 mg/kg for 10 days. Formulations containing pimozide have been used in the treatment of Tourette syndrome.

Химические свойства

White or almost white powder.

Использование

Pimozide is a D2 dopamine receptor antagonist that binds to the cloned 5-HT7 receptor with high affinity (1,2,3,4). Pimozide is also a Ca2+ channel antagonist. Pimozide is used as an antipsychotic.

Определение

ChEBI: Pimozide is a member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one in which one of the nitrogens is substituted by a piperidin-4-yl group, which in turn is substituted on the nitrogen by a 4,4-bis(p-fluorophenyl)butyl group. It has a role as a H1-receptor antagonist, a serotonergic antagonist, a first generation antipsychotic, an antidyskinesia agent and a dopaminergic antagonist. It is a member of benzimidazoles, an organofluorine compound and a heteroarylpiperidine.

Общее описание

Pimozide, 1-[1-[4,4-bis(p-fluorophenyl)butyl]-4-piperidyl]-2-benzimidazolinone (Orap), isa white to creamy white solid (pK_a＝9.42). Pimozide is 50%absorbed after oral administration. It is metabolized byCYP450 enzymes, in particular the CYP3A4 and CYP1A2isozymes, to inactive metabolites. Pimozide is excreted in theurine and to a lesser extent in the feces. Toxic effects may beproduced with pimozide in the presence of inducers or inhibitorsof CYP3A4 and CYP1A2. Pimozide is also a stronginhibitor of CYP2D6 without appearing to be an importantsubstrate of this isoform.99 The use of pimozide in the UnitedStates is small, but it is a critical drug for many patients withGilles de la Tourette disorder who cannot tolerate haloperidol.

Биологическая активность

Dopamine D 2 -receptor antagonist and antipsychotic which binds with very high affinity to the cloned rat 5-HT 7 receptor (K i = 0.5 nM).