Antipsychotic —abaperidone
Around 1% of the population are believed to suffer from schizophrenia to some degree. It is a severe mental disorder, with sufferers typically experiencing loss of contact with reality and a breakdown in mental processes.
The standard treatment is with antipsychotic drugs such as haloperidol or chlorpromazine, which have an effect, but do not improve the more negative symptoms of the condition, such as social withdrawal and apathy. Their side-effects are also a problem, notably extrapyramidal effects.1 These drugs act as antagonists at the D2 receptors in the brain's mesolimbic system, and there is a theory that the side-effects largely result from dopamine antagonism elsewhere in the brain.2
A major advance in therapy was made with the introduction of clozapine, the first of the atypical antipsychotics, which is effective in the management of the negative symptoms as well as the positive.3 It produces few extrapyramidal side-effects, but its other side-effects restrict its usefulness.
The search for further atypical antipsychotics has generated abaperidone.4 This promising compound appears to combine antipsychotic activity with reduced incidence of extrapyramidal side-effects, and is being investigated as a potential treatment for schizophrenia.
The compound binds to numerous different CNS receptors in addition to D2, and it is the greater affinity for 5-HT2 which is believed to lead to an improved side-effect profile. It also has a high affinity for D3 receptors. It is possible that D3 antagonism could be a better drug target for atypical antipsychotic medicines.
Abaperidone has been shown to be potent in animal models of schizophrenia, and clearly has potential as a new antipsychotic.5 Its safety and efficacy are currently being evaluated in clinical trials, and it could well prove to be a useful addition to the arsenal of treatments for schizophrenia.