[Characteristics of reactions of target enzymes of drugs containing new active ingredients (NAIs) and changes of the NAIs approvals over three decades from 1980 to 2009 in Japan].

We analyzed the target enzymes of drugs containing new active ingredients (NAIs) focusing on the characteristics of the reaction of the enzymes, and attempted to prepare a comprehensive overview of the changes in the approval of the drugs over a 3 decade period from 1980 to 2009 in Japan. Fifty-eight enzyme therapeutic targets of 235 NAIs were found to be primarily distributed to EC1, EC2 and EC3 classes, and the enzymes were unevenly distributed to 21 of 64 sub-classes and 34 of 264 sub-subclasses, respectively, classified by the enzyme nomenclature of the International Union of Biochemistry and Molecular Biology (IUBMB). Though the number of NAIs approved that targeted EC1 class enzymes decreased over the time frame studied, the number of NAIs which targeted EC2 class enzymes increased over the same time. There was no clear change in the number of NAIs which targeted other classes of enzymes. More than 80% of NAIs targeted one enzyme as a primary target, and less than 20% of NAIs targeted more than two enzymes as secondary targets. NAIs which primarily targeted EC2 and EC3 class enzymes had more secondary target enzymes than other classes. The results of this study revealed the characteristics of the reactions of the target enzymes of NAIs and the changes in NAI approvals in Japan during the three decades studied, and provided information regarding possible future trends of NAIs.

[New drug approvals over three decades from 1980 to 2009 in Japan--their therapeutic targets and biochemical properties].

We analyzed the therapeutic target molecules and biochemical properties of 893 new drugs with new molecular entities approved over three decades from 1980 to 2009 in Japan. According to our analysis of the therapeutic targets, 26.2% of new drugs were enzymes. Membrane receptors were found to be the second-most frequent molecular targets of the new drugs, representing 25.3% of the new drugs approved. The biochemical properties of the drugs were found to have changed over time. Though the total number of new drugs approved from the year 2000 was smaller than that in the 1980s and 1990s, the number of new protein drugs approved in the 2000s, largely recombinant bioactive substances and monoclonal antibodies, increased significantly compared with those approved in the 1980s and 1990s. The results obtained in this study indicated changes in the therapeutic targets, biochemical properties and therapeutic areas of new drugs approved over the last 30 years and suggest the aspects of the future development of new drugs.

Fear of negative evaluation is associated with delusional ideation in non-clinical population and patients with schizophrenia.

PURPOSE: A number of recent studies suggest that delusions may be explained as a continuum from normal beliefs. Fear of negative evaluation from others (FNE) is one of potential factors that might describe this psychological process of delusions. METHODS: In order to examine whether FNE is associated with delusional ideation in both non-clinical population and patients with schizophrenia, two sets of data [from a non-clinical student sample (n = 282) and from patients with schizophrenia (n = 117)] were collected to examine whether Brief Fear of Negative Evaluation Scale (BFNE) score and the 21-item Peters Delusions Inventory (PDI-21) score were associated with each other. Linear regression analyses were carried out to assess if the BFNE score still remained associated with the PDI-21 scores once the confounding effects of depression were controlled. RESULTS: BFNE scores were significantly related to PDI-21 scores in both non-clinical [Pearson product-moment correlation coefficient (r) = 0.37, 95% confidence Interval (CI) = 0.25-0.48] and patient (r = 0.33, 95% CI = 0.14-0.49) samples. These associations were still significant when confounding effects of depression were controlled. Standardised coefficients for the BFNE scores in the linear regression model were 0.21 in the student sample and 0.19 in the clinical sample. CONCLUSIONS: FNE was associated with delusional ideation both in non-clinical population and in patients with schizophrenia. FNE might be a potential target for both pharmacological and psychological interventions for patients with delusions.