[Development of new therapeutic drugs based on the pathophysiology of schizophrenia]

Cognitive deficits in schizophrenia are the core symptoms of this disorder, and are strongly correlated with decreased QOL in patients. Antipsychotic drugs have been used therapeutically for positive symptoms, including hallucinations and delusions. However, many patients treated with antipsychotic drugs fail to recover from cognitive deficits. Therefore, a number of new therapeutic drugs for cognitive deficits in schizophrenia are currently being developed around the world. A number of studies suggest that nicotine, a major component of cigarettes, could improve cognitive deficits in patients with schizophrenia. Accumulating evidence suggests that the alpha7 subtype of nicotinic receptors (alpha7 nAchRs) play a role in the pathophysiology of schizophrenia, as well as deficits in auditory evoked potential P50 in patients with schizophrenia. We have reported that the antiemetic drug tropisetron (alpha7 nAchR agonist and 5-HT3 receptor antagonist) improved auditory P20-N40 deficits in DBA/2 mice, and cognitive deficits after administration of the NMDA receptor antagonist phencyclidine. Furthermore, a single administration of tropisetron was associated with improved auditory P50 deficits in non-smoking patients with schizophrenia. Moreover, a randomized, double-blind, placebo-controlled study demonstrated that tropisetron significantly improved auditory P50 deficits and attention deficits in patients with schizophrenia. In this paper, the author will discuss the therapeutic potential of alpha7 nAChR agonists for cognitive deficits in patients with schizophrenia.