Belaperidone (Knoll AG)

Knoll is developing belaperidone, an antipsychotic agent, as a potential new treatment for schizophrenia. Phase II trials have commenced in Germany [200089,333710]. The compound is regarded as an atypical antipsychotic, similar in profile to clozapine, with potential to help patients whose illness has become difficult or impossible to treat. In rats, cumulative doses of belaperidone (0.128 to 32.768 mg/kg) reversed inhibition of the firing rate in the substantia nigra dopaminergic neurons induced by iv quinpirole. The ED50 value for the inhibition was 1.66 mg/kg, which is twice as potent as clozapine and 40-fold less potent than haloperidol. The drug did not produce catalepsy [346021]. In addition to possessing high affinity for 5-HT2 receptors (Ki = 3.3 nM), belaperidone selectively antagonizes the dopamine D4 (Ki = 3.1 nM) receptor, in preference to the D2 (Ki = 105 nM) subtype [247874]. It also has very low muscarinic affinity (Ki > 200 nM) [289024], [333710].