Memantine hydrochloride is only the anti-Alzheimer drug blocking the N-methy l-D-aspartate (NMDA) receptors, which are the subtypes of glutamate receptors, and has been available in Japan, 2011. Memantine hydrochloride protects neurons by means of suppressing the activation of NMDA receptors by excessive glutamate. Moreover, memantine hydrochloride prevents and suppress the behavioral psychological symptoms of dementia such as aggressiveness and behavioral disturbances. Memantine hydrochloride is not metabolized by CYPs, and quite safe because major side effects are dizziness, constipation, weight loss, headache. Because the mechanism of memantine hydrochloride is different from that of donepezil hydrochloride, memantine can be prescribed with cholinesterase inhibitors. Those reasons indicate that memantine will be one of the major pharmacotherapies of AD.

View full abstract

Amyloid vaccine therapy aims to reduce amyloid burden in AD brain and to protect neuronal cell death. Although AN1792 vaccine has been confirmed to reduce amyloid, the therapy has caused meningoencephalitis. Currently, the safer vaccine, Bapineuzumab, is on the phase III clinical trials. There are two injection ways, antigen or antibodies, for decreasing amyloid. Monitoring vasogenic edema by brain MRI is the key to continue Amyloid vaccine therapy. It is one of the problems that there might be some AD patients with severe BPSD to monitor brain MRI in the future. Carrying Apolipoprotein E4 would be the risk factor for vasogenic edema. Other biological biomarkers evaluating the risk for vasogenic edema should be investigated.

View full abstract

[in Japanese]

View full abstract

It came to be able to use three kinds of acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease. In the metaanalysis study there is no significant difference in improvement of cognitive function between these three acetylcholinesterase inhibitors. However, the pharmacological action, indication, medicinal form, frequency of administration and the period to reaching the maintenance dose are different in these three medicine. Sufficient assessment of patients condition need to selection and changing in these medicine for the treatment of Alzheimer’s disease.

View full abstract

Attention-deficit hyperactivity disorder (ADHD) is a debilitating disorder that is characterized by developmentally subaverage levels of inattention, impulsivity and motor restlessness. Although the neurocognitive accounts for the etiology and pathophysiology of ADHD had been centered on executive dysfunctions, such as poor behavioral inhibition and cognitive interference control, recent conceptualizations of ADHD further incorporate abnormalities in the reward system, primarily in an attempt to understand the impulsive aspect of the disorder. Here we will review recent neuroimaging studies that investigated the compromised reward circuitry in patients with ADHD and how the altered functionality could be related to the symptomatology of this disorder.

View full abstract

Patients of schizophrenia have the thought disorder. We expected that one of the implicit and explicit decision making systems error, task set error and self cognition error caused the thought disorder in patients of schizophrenia. In this article, therefore we explain the neural mechanisms and role of these three systems for thought processing.

View full abstract

G-protein-activated inwardly rectifying potassium channel (GIRK channel) mediates the signaling of various addictive substances. Four GIRK channel subunits (GIRK1~4) have been identified in mammals ; GIRK1~3 subunits are widely distributed in the central nervous system, and GIRK4 subunit is distributed primarily in the heart. The present review examines roles of GIRK channels in the reward system. The results of review indicate that (1) the difference in genetic sequence of GIRK2 subunit is associated with opioid sensitivity, (2) fluoxetine, paroxetine and ifenprodile, but not fluvoxamine, inhibit GIRK channel and reduced methamphetamine preference, and (3) the medications with GIRK channel-inhibitory capacity appear to exert a curing effect on substance dependence based on retrospective studies. Above findings suggest that GIRK channels may be key molecules in the reward system, and are expected to become target molecules for treatment of substance dependence.

View full abstract

Oxidative stress is a central mediator of advanced glycation end products (AGEs) formation, and pyridoxamine (one of three components of vitamin B6) is known to detoxify reactive carbonyl compounds (RCOs). Toxic RCOs such as methylglyoxal, glyoxal, and 3- deoxyglucosone are formed from sugars, lipids, and amino acids. Accumulation of such RCOs, referred to as carbonyl stress, results in the modification of proteins and the eventual formation of AGEs such as pentosidine. In this study, we found that a certain subtype of schizophrenic patients exhibit idiopathic carbonyl stress with high plasma pentosidine levels and depletion of vitamin B6 in spite of no physical complications. Carbonyl stress is a new target of medication for schizophrenia without neurotransmitter based concept of therapeutics and inhibiting the carbonyl stress by pyridoxamine is expected to cure negative symptoms and treatment-registrant cases using conventional medications. In particular, the markedly high pentosidine level in schizophrenic patients with low vitamin B6 level suggest that pyridoxamine may prove clinical useful.

View full abstract

Cognitive bias, a specific pattern of information processing such as interpretation of ambiguous information in a negative way and captured attention to negative stimulus, is often seen in anxious and depressive individuals. Such cognitive biases have been considered to lead clinically significant anxiety and depression. A cognitive bias modification program (CBM) that aims to modify a cognitive bias thereby reducing anxiety and depression has been developed by transforming a computer-based program used for cognitive bias measurement. A recent meta- analysis has revealed that the CBM does have an effect of alleviating anxiety and depression and that its effect is largely influenced by programming parameters (e. g., duration of stimulus presentation and types of stimulus). In this review, based on recent meta- analytic findings on a relationship between cognitive bias and anxiety/depression, we will provide optimal parameters for methodological elaboration of existing cognitive bias measurement programs and eventually for further development of CBMs.

View full abstract