Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
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In recent years, many analogs of narcotics have been widely distributed as easily available psychotropic substances and have become a serious problem in Japan. To counter the spread of these non-controlled substances, the Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new category; Designated Substances in order to more strictly control these substances. In April 2007, 31 compounds and 1 plant were first controlled as Designated Substances. ⋯ They were 13 tryptamines, 17 phenethylamines, 11 cathinones, 4 piperazines, 23 synthetic cannabinoids, 6 alkyl nitrites, 3 other compounds and 1 plant. In this review, we show our survey of the spread of new designer drugs in Japan, focusing especially on synthetic cannabinoids and cathinone derivatives. Also, the prevalence and legal status of these substances in other countries will be presented.
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A growing body of evidence indicates that extracellular nucleotides released or leaked from non-excitable cells as well as neurons play important roles in the regulation of neuronal and glial functions in the whole body through ATP receptors. ATP receptors (ionotropic P2X and metabotropic P2Y receptors) are the most abundant receptor families in living organisms. In the central nervous system, these receptors participate in synaptic transmission and in intercellular communications between neurons and glia. ⋯ P2X4 receptors expressed in microglia in particular play a critical role in neuropathic pain signaling. The expression and activity of P2X4 receptors are up-regulated and enhanced predominantly in activated microglia in the spinal cord where damaged sensory fibers project. These findings provide novel targets for developing new medicines to treat neuropathic pain.
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Schizophrenia is characterized by various behavioral abnormalities including cognitive dysfunction. Neonatal ventral hippocampus (NVH)-lesioned rats had been known as neurodevelopmental animal model similar to schizophrenia. Previous observations indicate that postpubertal NVH-lesioned rats exhibit impairments in prepulse inhibition (PPI), spontaneous locomotion, social interaction behavior and working memory. ⋯ Since Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), which is NMDA receptor downstream kinase, is essential for memory and learning acquisition, we developed a protocol to monitor the spatial changes in CaMKII autophosphorylation using immunohistochemical imaging of whole brain slices with anti-autophosphorylated CaMKII antibody in order to address mechanisms underlying impaired cognitive function in NVH-lesioned rats. Immunohistochemical analyses using anti-autophosphorylated CaMKII antibody revealed that CaMKII autophosphorylation was significantly reduced in the medial prefrontal cortex (mPFC) of NVH-lesioned rats compared with control animals. This immunohistochemical technique is useful to investigate temporal and special changes in CaMKII activity in rodent brain and to evaluate drugs to improve the cognitive impairment.
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The drug-drug interactions of tizanidine and cytochrome (CYP) P450 1A2 inhibitors, which potentially alter the hepatic metabolism of tizanidine, were investigated by retrospective survey of medical records with regard to prescription. One thousand five hundred sixty-three patients treated with tizanidine at University of Tsukuba Hospital were investigated. Of those, 713 patients (45.6%) were treated with coadministration of tizanidine and CYP1A2 inhibitors (37 drugs). ⋯ Adverse effects (e.g., drowsiness: 10 patients; low blood pressure: 9 patients; low heart rate: 9 patients) were observed in 23 patients (23%) 8±10 days after CYP1A2 inhibitors were coadministered. The patients with tizanidine-induced adverse effects were of older age (64.3±9.8 vs. 57.5±18.1 years, p<0.05) and received a higher daily dose of tizanidine (3.00±0.74 vs. 2.56±0.86 mg/day, p<0.05) than the patients without adverse effects. The present results suggest that coadministration of tizanidine and CYP1A2 inhibitors enhances tizanidine-induced adverse effects, especially in elderly patients treated with a higher dose of tizanidine.
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Under new courses of study, medicine-related content has been incorporated into health and physical education at junior high schools, and classes on the "Correct use of medicine" began as part of this content in 2012. Based on the "School Health and Safety Law" implemented in April 2009, health guidance provided by school physicians, pharmacists, and dentists has also been incorporated. This has raised expectations that educational programs concerning the "Correct use of medicine" could be effectively implemented through cooperation between school pharmacists and health and physical education teachers. ⋯ It consisted of an introduction (7 min), a development portion (35 min), and a conclusion (8 min). After the class, a question and answer session was held with observers (n=11) and a questionnaire survey, which resulted in high evaluations, was conducted on the students. Comments including concern over the large volume of educational content and the need to raise awareness were heard, but the results of the questionnaire survey showed that many students found the class content useful and interesting.