Editorial [Hot topic: The Search of Targets for Novel Antipsychotic Drugs (Executive Editor: Akihiro Takano)]

Schizophrenia is a psychiatric disorder demonstrating a combination of positive symptoms such as delusions and hallucinations, negative symptoms such as apathy and lack of emotion, and cognitive dysfunctions. The etiology is still unknown although there are several hypotheses such as dopamine/glutamate hypothesis. Since chlorpromazine was found to be effective for the treatment of the patients with schizophrenia over 50 years ago, the first-generation antipsychotics have demonstrated clinical efficacy mainly for positive symptoms. The main target of these antipsychotics was dopamine D2 receptor. With the introduction of the second-generation antipsychotics, side effects such as extrapyramidal symptoms, which were often observed with high doses of the first-generation antipsychotics, have been reduced. On the other hands, other side effects such as weight gain and metabolic abnormalities, have emerged, and clinical efficacy with these drugs has not been enough especially for negative symptoms and cognitive impairment. Cognitive dysfunctions are one of the critical issues to determine the morbidity of schizophrenia. Although a common main target has been dopamine D2 receptor regardless of the generation of antipsychotics, other potential targets should be investigated for the development of novel antipsychotics. In this issue, current progress and future prospects of these potential targets for novel antipsychotic drugs were reviewed. Neuronal nicotinic acetylcholine receptors (nAChR) are expected to play a role for the cognitive dysfunction. Different functions have been reported by different subtypes of nAChR. Radek et al. [1] reviewed the possibility of the alpha4 beta2 nAChR agonists for the treatment of schizophrenia. Thomsen et al. [2] reviewed the neurological properties and the cognitive effects of alpha7 nAChR activation for the drug development. Neurokinin receptors, which were considered to be related with emotional functions, are another line of important targets. Dawson and Smith [3] reviewed the neurokinin receptors widely, and preclinical and clinical findings about NK3 receptor, which is relevant to the drug development for schizophrenia. In psychiatric diseases such as schizophrenia, it is not easy to establish the animal models. One of the successful animal models for the screening of antipsychotics is the condition avoidance response (CAR) test. Wadenberg [4] reviewed the significance, accuracy and use of the CAR test as a screening tool in current and future antipsychotic drugs. The measurement of the in vivo receptor occupancy by drugs has yielded the information relevant to dose selection and pharmacokinetics of antipsychotics. Takano [5] reviewed the utility of PET technique in the development and evaluation of novel antipsychotics. I hope this issue would help the readers to understand the current and future directions of the drug development for the treatment of schizophrenia.