adrenoceptors are targets for antipsychotic drugs

Rationale Almost all antipsychotic drugs (APDs), irrespective of whether they belong to the first-generation (e.g. haloperidol) or second-generation (e.g. clozapine), are dopamine [D.sub.2] receptor antagonists. Second-generation APDs, which differ from first-generation APDs in possessing a lower propensity to induce extrapyramidal side effects, target a variety of monoamine receptors such as serotonin (5-hydroxytryptamine) receptors (e.g. [5-HT.sub.1A], [5-HT.sub.2A], [5-HT.sub.2C], [5-HT.sub.6], [5-HT.sub.7]) and [α.sub.1]-and [α.sub.2]-adrenoceptors in addition to their antagonist effects at [D.sub.2] receptors. Objective This short review is focussed on the potential role of [α.sub.2]-adrenoceptors in the antipsychotic therapy. Results Schizophrenia is characterised by three categories of symptoms: positive symptoms, negative symptoms and cognitive deficits. [α.sub.2]-Adrenoceptors are classified into three distinct subtypes in mammals, [α.sub.2A], [α.sub.2B] and [α.sub.2C]. Whereas the [α.sub.2B]-adrenoceptor seems to play only a minor role in the brain, activation of postsynaptic [α.sub.2A]-adrenoceptors in the prefrontal cortex improves cognitive functions. Preclinical models such as D-amphetamine-induced locomotion, the conditioned avoidance response and the pharmacological N-methyl-D-aspartate receptor hypofunction model have shown that [α.sub.2C]-adrenoceptor blockade or the combination of [D.sub.2] receptor antagonists with idazoxan ([α.sub.2A/2C]-adrenoceptor antagonist) could be useful in schizophrenia. A potential benefit of a treatment combination of first-generation APDs with the [α.sub.2A/2C]-adrenoceptor antagonists idazoxan or mirtazapine was also demonstrated in patients with schizophrenia. Conclusions It is concluded that [α.sub.2]-adrenoceptors may be promising targets in the antipsychotic therapy. Keywords Nucleus accumbens * Prefrontal cortex * Schizophrenia * [D.sub.2] receptor antagonists * [α.sub.2]-Adrenoceptor agonists * [α.sub.2]-Adrenoceptor antagonists