Marijuana has been used as a traditional medicine and a pleasure-inducing drug for thousands of years around the world, especially in Asia. Δ9-Tetrahydrocannabinol, major psychoactive component of marijuana, has been shown to interact with specific cannabinoid receptors, thereby eliciting a variety of pharmacological responses in experimental animals and human. In 1990, the gene encoding a cannabinoid receptor (CB1) was cloned. This prompted the search for endogenous ligands. In 1992, N-arachidonoylethanolamine (anandamide) was isolated from pig brain as an endogenous ligand, and in 1995, 2-arachidonoylglycerol was isolated from rat brain and canine gut as another endogenous ligand. Both anandamide and 2-arachidonoylglycerol exhibit various cannabimimetic activities. The results of structure-activity relationship experiments, however, revealed that 2-arachidonoylglycerol, but not anandamide, is the intrinsic natural ligand for the cannabinoid receptor. 2-Arachidonoylglycerol is a degradation product of inositol phospholipids that links the function of the cannabinoid receptors with the enhanced inositol phospholipid turnover in stimulated tissues and cells. The possible physiological roles of cannabinoid receptors and 2-arachidonoylglycerol in various mammalian tissues such as those of the nervous and inflammatory cells are demonstrated. Furthermore, the future development of therapeutic drugs coming from this endocannabinoid system are discussed.
The aim of this study was to discuss subject selection and the evaluation method for an objective structured clinical examination (OSCE) in pharmaceutical sciences. We designed the OSCE to assess pharmaceutical students' clinical ability. In this trial, there are three stations (ST①: dispensing powdered medicine, ST②: patient reception, ST③: drug counseling), and 25 students and six instructors participated. Each student took an examination at two stations, and evaluated other students at the other station. Each instructor evaluated the student at two stations. Before the evaluation, we developed a checklist that contained the items “evaluation of the quantity” of the action, “evaluation of the quality” of the skill and the attitude, and “overall evaluation” to ensure the standardization of scoring. After the OSCE trial, we calculated and analyzed each examinee's evaluation score. In ST① and ST③, the average time for performance exceeded the time limit (5 min). There was no significant relationship between the each examinee's evaluation score and the time at all stations. The evaluation point “evaluation of the quantity” did not differ among evaluators, but a difference was seen in the “evaluation of the quality.” In addition, in the quantitative evaluation, there was a difference in the evaluation of the item for which the evaluator's judgment was necessary. Instructors' evaluations were more severer than students'. In the “overall evaluation,” there was no significant relation between the quantitative evaluation score and the score of the overall impression. However, there was a significant relationship with the qualitative evaluation. From these results, for assignment making, it is necessary for examinees to finish the work within the time limit, and that the evaluation not affect the performance time. Additionally, it is necessary to standardize the evaluation to reduce differences among evaluators, who should be trained. Moreover, it was suggested that the selection of an appropriate evaluation system for each evaluation item is important in OSCE stations.
Meloxicam (MLX), a non-steroidal anti-inflammatory drug (NSAID) and a selective COX-2 inhibitor is a water insoluble drug (about 12 μg/ml). In order to improve the aqueous solubility of the drug and its dissolution rate, physical mixture and solid dispersions with skimmed milk were prepared and investigated. Enhancement of aqueous solubility of MLX was observed with solid dispersion of the drug with skimmed milk due to amino acids and surface active agents content in the milk, which can be used for the treatment of gastric disturbance. Rotary vacuum evaporation technique was used to prepare solid dispersion. Results showed that the solubility of solid dispersion of the drug was almost three times greater than the pure drug. Similarly, the solid dispersion of the drug indicated a significant improvement in the dissolution of the drug as compared to the physical mixture and the pure drug. Differential scanning calorimetry, X-ray diffraction and scanning electron microscopic analysis revealed the formation of solid dispersion of the drug with skimmed milk.
The reactions of 2- or 4-cyanopyridinium salts with active methylene compounds such as dimethyl malonate, malononitrile, and cyclohexane-1,3-dione affording 2- or 4-(substituted methylene) pyridines are described. Similar reactions of 4-cyano-2-methylthiopyridinium and 4-cyano-2-methylthioquinolinium salts, both of which have two leaving groups, were readily prepared from 4-cyano-1-methyl-2(1H)-pyridone and 4-cyano-1-methyl-2(1H)-quinolone via 4-cyano-1-methyl-2(1H)-thiopyridone and 4-cyano-1-methyl-2(1H)-thioquinolone in two steps, proceeding at the 2- and/or 4-positions on the pyridine or quinoline rings.
The carbon-carbon bond-forming reactions of 1-methyl-2-methylthiophenylpyridinium iodides with active methylene compounds (such as dimethyl malonate, malononitrile) using NaH as a base gave the 2-substituted methylene-1,2-dihydropyridine derivatives.
The noradrenalin and serotonin re-uptake inhibitor venlafaxine has an analgesic effect that is independent of its antidepressant activity; however, the mechanism of this effect remains to be elucidated. This study was performed to investigate the possible roles of the opioidergic system and nitric oxide (NO) pathway in the analgesic effect of venlafaxine. Eighty Wistar rats of both sexes were allocated to 10 groups. The hot plate test was used to assess the antinociceptive/analgesic effect. The temperature of the hot plate was adjusted to 52.5±1°C, the cut-off period was set to be 50 sec; licking of the hind paw was used as a sign of pain perception. Venlafaxine alone (25 mg/kg) showed marked analgesic activity (p<0.05). N-ω-nitro-L-arginine (L-NOARG) alone (20 mg/kg) and naloxone alone (2 mg/kg and 4 mg/kg) showed no analgesic activity (p>0.05). Coadministration of low-dose naloxone (2 mg/kg) and both doses of L-NOARG (20 and 40 mg/kg) with venlafaxine (25 mg/kg) did not modify the analgesic effect but high-dose naloxone (4 mg/kg) decreased it significantly (p<0.05). In conclusion, these results suggest that the opioidergic system but not the NO pathway has a role in the analgesic effect of venlafaxine.
To evaluate differences in viewpoints and awareness between patients with and without a “family pharmacy”, we performed a questionnaire survey. The questionnaire consisted of 21 questions including “I often read books and journals about health.” and “Patients have the right of being informed of the medical treatment they receive”. The degree of applicability was selected among 6 grades(“definitely inapplicable”—“definitely applicable”). The subjects were classified into 3 groups “without a family pharmacy”, “with a regular pharmacy for each hospital/clinic” and “with a family pharmacy”, and factor analysis was performed. As a result, 5 factors were extracted in each group. However, the order of the 2nd—4th factors differed among the 3 groups. Paying attention to these differences, we found that patients “with a family pharmacy” have resolved doubts about or dissatisfaction with medical care to some extent.