著者

有富 正和

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.82, no.5, pp.771-773, 1962-05-25 (Released:2010-02-19)

参考文献数

12

被引用文献数

1 3

---

Astragalin was isolated and identified from the flower petals of Rosa multiflora THUNB. Astragalin and trifolin were separated and identified from the flower petals of Rubus hirsutus THUMB.

著者

正山 征洋

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.127, no.10, pp.1593-1620, 2007-10-01 (Released:2007-10-01)

参考文献数

92

被引用文献数

4 4

---

In order to quality control for medicinal plants such as Aconitum charmicaelii, Rhemannia glutinosa, Atractyrodes lancea, Pinellia ternata, Panax species and Gentiana scabra were clonally micropropagated by tip tissue culture and embryogenetic techniques. Monoclonal antibodies against the bioactive compounds contained in the crude drugs were prepared and set up the ELISA as a high sensitive and quick determination method. A newly developed eastern blotting methodology can stain typically the only antigen molecule and the related compounds having a same aglycone. Knockout extract can be prepared by using an immunoaffinity column conjugated with monoclonal antibody, and its importance has been discussed. Single chain fragment-variable gene against solamargine was cloned and transformed to a host plant, Solanum chasianum resulting in the increase of antigen molecule as 2.5 to 3 times. Three biosynthetic enzymes regarding marihuana compounds, THCA-, CBDA-, CBCA-synthases were isolated. THCAsynthase was cloned, over expressed and confirmed its characteristics including FAD combining enzyme, and finally determined the structure by X-ray analysis. The distribution of THCAsynthase was also investigated using its and GFP hybrid gene. We found new functions for saffron like improving learning and memory and LTP for blocking by ethanol. A folk medicine in Taiwan, Anoectochilus formosanus was propagated in vitro and investigated opening new pharmacological activities in lipid methabolism.

著者

北 泰行

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.122, no.12, pp.1011-1035, 2002-12-01 (Released:2003-02-18)

参考文献数

109

被引用文献数

13 17

---

Biologically active natural products with unique, highly complex molecular skeletons have been used as leading compounds for raw materials of new drugs. Due to the limitations of natural supply, highly efficient, large-scale syntheses and molecular design have been sought in drug discovery. For this purpose, we have focused on a synthetic strategy effective in developing novel reactions and reagents and found several useful regio- and stereospecific reactions, contributing to the synthesis of otherwise unattainable target molecules. The application of these reactions for the total synthesis of three types of potent cytotoxic natural products for the first time is described in this paper. The basic concept is first described. Then the total synthesis of anthracyclines, fredericamycin A, and discorhabdins is reported. Novel reactions using hypervalent iodine reagents under environmentally benign conditions are also described. The future prospects for this method are discussed.

著者

矢野 育子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.10, pp.1227-1234, 2019-10-01 (Released:2019-10-01)

参考文献数

31

---

Pharmacometrics is the mathematical study of pharmacokinetics, disease progression, and clinical outcomes. One objective of pharmacometrics is to facilitate rational drug treatment in patients, also termed clinical pharmacometrics. In this review, our clinical pharmacometric studies conducted over the last 10 years are discussed. Population pharmacokinetic analysis using therapeutic monitoring data for levetiracetam revealed that oral clearance allometrically scaled to both body weight and estimated glomerular filtration rate can accurately predict clinical data from patients of various ages (pediatric to elderly) with varying renal function. Dosage adjustments based on renal function in the package information are effective in controlling the trough and peak concentrations in similar ranges. In addition, a retrospective pharmacokinetic and pharmacodynamic study revealed that the efficacy of low-dose clobazam therapy was significantly influenced by CYP2C19 polymorphisms. Pharmacokinetic and pharmacodynamic models were successfully built using electronic medical information to explain retrospective international normalized ratio values of prothrombin time before and after catheter ablation in warfarin-treated patients. Simulation studies suggest that more than 20 mg of vitamin K2 is unnecessary in the preoperative period of catheter ablation. A physiologically based pharmacokinetic model adapted to tacrolimus pharmacokinetic data in patients who underwent living-donor liver transplantation was constructed, and clarified that oral clearance of this drug was affected by CYP3A5 genotypes in both the liver and intestine to the same extent. In conclusion, pharmacometrics is a useful methodology for individualized and optimized drug therapy.

著者

恩田 光子 高垣 伸匡

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.5, pp.645-647, 2018-05-01 (Released:2018-05-01)

参考文献数

3

被引用文献数

3

---

Osaka University of Pharmaceutical Sciences has included an evidence-based medicine (EBM) exercise in the introductory education for clinical practice for 4th-year pharmacy students since 2015. The purpose of this exercise is to learn the process of practice and basic concepts of EBM, especially to cultivate the practical ability to solve patients' problems and answer their questions. Additionally, in 2016, we have attempted flipped teaching. The students are instructed to review the basic knowledge necessary for active learning in this exercise by watching video teaching materials and to bring reports summarizing the contents on the flipped teaching days. The program includes short lectures [overview of EBM, document retrieval, randomized controlled trials (RCTs), and systematic review], exercises [patient, intervention, comparison, outcome (PICO) structuring, critical appraisal of papers in small groups with tutors], and presentations. The program includes: step 1, PICO structuring based on scenarios; step 2, critical appraisal of English-language papers on RCTs using evaluation worksheets; and step 3, reviewing the results of the PICO exercise with patients. The results of the review are shared among groups through general discussion. In this symposium, I discuss students' attitudes, the effectiveness of small group discussions using flipped teaching, and future challenges to be addressed in this program.

著者

清水 忠 安原 智久

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.5, pp.629, 2018-05-01 (Released:2018-05-01)

著者

金子 雅幸

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.6, pp.805-809, 2016-06-01 (Released:2016-06-01)

参考文献数

26

被引用文献数

2 6

---

Studies on endoplasmic reticulum (ER)-associated degradation (ERAD), in which unfolded proteins accumulated in the ER are selectively transported to the cytosol for degradation by the ubiquitin-proteasome system, have been focused on molecular mechanisms in yeast. In human, disruption of the ER quality control system causes various diseases, such as neurodegenerative disease, lifestyle disease, and cancer. However, there are many ERAD genes with unknown physiological and pathological functions. We identified the novel ubiquitin ligase HRD1 involved in ERAD. HRD1 is expressed in brain neurons and protects against ER stress-induced apoptosis. In familial Parkinson's disease, accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), a substrate of ubiquitin ligase Parkin involved in ERAD, causes ER stress and apoptosis. We demonstrated that HRD1 promotes ubiquitination and degradation of Pael-R and suppresses ER stress and apoptosis induced by Pael-R. Amyloid precursor protein (APP) is processed into amyloid β (Aβ) in Alzheimer's disease. We found that HRD1 promotes APP ubiquitination and degradation, resulting in decreased generation of Aβ. Furthermore, suppression of HRD1 expression causes APP accumulation and Aβ generation associated with ER stress and apoptosis. Interestingly, HRD1 protein levels significantly decreased in the cerebral cortex of Alzheimer's disease patients, possibly because of its insolubilization. We demonstrated that HRD1 protein was insolubilized by oxidative stress, resulting in the accumulation of HRD1 into the aggresome. In conclusion, oxidative stress-induced HRD1 insolubilization might be involved in a vicious cycle of increased Aβ production and Aβ-induced oxidative stress in Alzheimer's disease pathogenesis.

著者

澁谷 正俊

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.10, pp.1131-1143, 2012-10-01 (Released:2012-10-01)

参考文献数

55

被引用文献数

2 4

---

Organic nitroxyl radical catalysts have recently attracted great attention because they realize efficient alcohol oxidation under mild and environmentally benign conditions. A representative of this class is 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO). We have also developed 2-azaadamantane N-oxyls (AZADOs) as highly efficient oxidation catalysts. These nitroxyl radicals are generally oxidized by a cooxidant to generate oxoammonium salts, which are active species for alcohol oxidation. In the oxidation systems presented in this paper, we focus on the differences between these two species in terms of oxidation state and counter anion. Herein, the effects of a counter anion of an oxoammonium species on its reaction selectivity are shown. On the basis of the control of the counter anion, we have developed catalytic oxidative rearrangement of tertiary allylic alcohols to β-substituted α,β-unsaturated carbonyl compounds. Moreover, we have developed novel useful oxidation systems utilizing a catalytic oxoammonium salt; namely, a one-pot oxidation of primary alcohols to carboxylic acids and an aerobic alcohol oxidation.

著者

中川 俊夫 森 芳夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.75, no.11, pp.1322-1325, 1955-11-25 (Released:2010-02-19)

参考文献数

7

---

Water-soluble vitamin E derivative was obtained by the reaction of α-tocopheryl dichlorophosphate and polyethylene glycol. The reaction product was purified through alumina chromatography and from the phosphorus content, ultraviolet and infrared absorption, average molecular weight, and the hydrolyzates, the product was assumed to be a mixed phosphate of α-tocopherol and polyethyleneglycol.

著者

川谷 豊彦 藤田 早苗之助 大野 忠郎 久保木 憲人

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.78, no.1, pp.58-61, 1958-01-25 (Released:2010-02-19)

参考文献数

6

---

1) It was found that the cultivation of Ammi visnaga LAM. in Japan should start with autumn sowing during the middle of October, at the latest, from the point of growth, yield of fruit, and content of khellin (Table I).2) The optimal soil moisture in the said cultivation seems to be in the range of 60-70% of the water capacity from the point of growth, yield of fruit, and khellin content (Table II).3) This plant grows favorably in the soil with pH ranging from 6.5 to 7.5, with neutral reaction as the median point.4) It was confirmed through experimental cultivation extending from 1951 to 1955 that the cultivation of this plant should be made in a place with small amount of rainfall during the summer and a well-drained soil rich in clay (Tables II and III).5) Comparative cultivation was carried out with five foreign strains with different origin (khellin content of the original seed, 0.61-0.94%) and the khellin content of the fruit from these cultivated plants was 0.32-0.51%, indicating a fair decrease of the content. However, this was thought to be due to the profuse generation of diseases during August, before flowering, and unhealthy fruit had been mixed (Table IV).6) In one individual plant, the fruits that ripened earlier seemed to have higher content of khellin (Table V).

著者

佐々木 正 兼松 顕 大瀬 誠子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.84, no.10, pp.977-983, 1964-10-25 (Released:2010-02-19)

参考文献数

22

---

Some diphenyl derivatives were visualized, imitating the A and C rings in the morphine skeleton with the C ring substituted with a phenyl group, as shown in Table I. On the assumption that the angle of A and C rings is necessary for these compounds to show analgesic action by their contact with the cells in the action site, examinations were made for the syntheses of 9-substituted 9, 10-dihydrophenanthrene and 5-substituted 9, 10-dihydro-5H-dibenzo [a, b] cycloheptene.1) 9, 10-Dihydro-9-phenanthrenecarboxylic acid (IV) was obtained in a good yield by the reduction of 9-phenanthrenecarboxylic acid (X) with sodium amalgam. Curtius reaction of the azide of IV afforded ethyl 9, 10-dihydro-9-phenanthrenecarbamate (XIV) but this substance was extremely labile and underwent decomposition on being left at room temperature to form phenanthrene. The acid amide compounds (XVII and XVIII) of IV were stable.2) Reaction of 5-amino-10, 11-dihydro-5H-dibenzo [a, b] cycloheptene (XXII) with methyl iodide in the presence of alkali gave 5-dimethylamino compound (XXIII). Amination of 10-bromo compound (XXV) was attempted in order to obtain 10-dimethylamino compound but the product was found to be 5H-dibenzo [a, b] cyclohepten-5-one (XXVI).

著者

奈女良 昭 西田 まなみ 屋敷 幹雄 木村 恒二郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.126, no.12, pp.1271-1277, 2006-12-01 (Released:2006-12-01)

参考文献数

12

被引用文献数

1 1

---

In emergency and critical care medicine, it is important to guess which poisons that patients have taken or been exposedto. The assumption and identification of save lives. Therefore an accurate screening system is required to treat acute poisoning patients in clinical toxicology. However, the ability of a medical center is not sufficient to analyze poisonous substances using analytical equipment. Moreover, the handling and maintenance of the equipment are tedious and costly. To improve these problems, a simple detection method should be established to identify poisons and to treat acute patients in emergency and critical care medicine. In our laboratory, various supports have been attempted for the training of analysts who cope with poisoning incidents and accidents due to toxic substances. Moreover, a simple detection method for toxic substances utilized in the medical center was developed without using expensive analysis apparatus. However, it is impossible to detect and identify chemical warfare agents in a clinical laboratory, because of possible secondary exposure to such dangerous substances in insufficient analytical laboratory equipment. Therefore it is necessary to contact related organizations possessing the proper facilities.

著者

堤 竹蔵 今井 俊吾 山田 勝久 山田 武宏 笠師 久美子 小林 正紀 井関 健

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.7, pp.1055-1061, 2019-07-01 (Released:2019-07-01)

参考文献数

20

被引用文献数

2

---

Linezolid (LZD), an antimicrobial agent against methicillin-resistant Staphylococcus aureus, demonstrates good bone and joint penetration, and is used for prosthetic bone and joint infections. Recently, we observed vomiting in several patients administered LZD. However, there are few reports on the incidence rate of, and risk factors for, LZD-induced nausea and vomiting. In this study, we aimed to verify the relationship between LZD administration and vomiting. Patients administered LZD at the Department of Orthopedic Surgery of Hokkaido University Hospital between November 2008 and December 2017 were enrolled in the study. The primary endpoint was the comparison of the vomiting rate between patients administered LZD (LZD group) and those administered other antibiotics (non-LZD group). For the secondary endpoint, to verify the risk factors of vomiting, a univariate logistic regression analysis was performed. In total, 130 patients were included in this study; 77 patients in the LZD group, and 53 in the non-LZD group. Vomiting occurred in 18 patients in the LZD group and 4 patients in the non-LZD group (23.4% and 7.5%, respectively); this was significantly higher in the LZD group. In the univariate logistic regression analysis, LZD administration, gender (female), age ≥65 years, renal impairment (creatinine clearance <60 mL/min) and concomitant use of rifampicin were extracted as potential risk factors of vomiting. The results of this study reveal a possible relationship between LZD administration and vomiting.

著者

鈴木 理珠 鈴木 匡 菊池 千草

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.7, pp.1047-1054, 2019-07-01 (Released:2019-07-01)

参考文献数

13

被引用文献数

4

---

In 2015, Japan's Ministry of Health, Labour and Welfare released a report on the need for pharmacies to support public health, although the details of such a service was left to each pharmacy. Consequently, pharmacists had to determine the nature of such services. We considered the services that pharmacists could offer to improve people's lifestyles. This study tests such a service at a pharmacy. We prepared a lifestyle self-review test. From September 2015 to February 2016, pharmacists interviewed members of the community using the test, and pharmacists at 50 pharmacies in Aichi prefecture, Japan, set goals for lifestyle improvement. We analyzed 289 tests. The number of people who had a dietary goal concerning snacking was reduced from 19 people who snacked every day to 11. The number of people who had a goal to reduce their drinking was reduced from 7 people who drank every day to 4. The number of people who had an exercise goal was reduced from 17 people who did not exercise every day to 7. The people who had a sleep goal increased the number of days in which they got adequate rest. Those who had specific, tangible goals for walking achieved their goal at a higher rate than did those who had a goal but no tangible elements, such as time spent or number of steps achieved. Overall, the lifestyle self-review at the pharmacy was effective for lifestyle improvement. Pharmacists should help people set goals with tangible elements to improve their lifestyle more effectively.

著者

福井 裕行

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.127, no.1, pp.15-25, 2007-01-01 (Released:2007-01-01)

参考文献数

18

被引用文献数

1 1

---

Histamine H1 receptors are down-regulated as one step in receptor desensitization. Five phosphorylation sites of the H1 receptor seem to play a key role in receptor down-regulation. In contrast, an increase in the H1 receptor expression level following its mRNA elevation was found in the nasal mucosa in hypersensitivity model rats. Up-regulation of the H1 receptor was induced by the direct stimulation of the H1 receptor. H1 receptor up-regulation was suppressed by pretreatment with antiallergic agents.

著者

山﨑 寛之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.5, pp.663-672, 2019-05-01 (Released:2019-05-01)

参考文献数

49

---

Marine environments offer a rich source of natural products with potential therapeutic applications because the ocean covers 70% of the earth's surface and approximately 80% of all living organisms live in the sea. Therefore we have investigated bioactive compounds from marine organisms such as marine sponges, ascidians, and marine-derived microorganisms. This review consists of two topics based on marine natural product chemistry. (1) Protein tyrosine phosphatase (PTP) 1B plays a key role as a negative regulator in the insulin and leptin signaling pathways. Accordingly, the development of PTP1B inhibitors is expected to provide new drugs for type 2 diabetes and obesity. We have been searching for new types of PTP1B inhibitors among marine organisms and identified various PTP1B inhibitors from marine sponges and fungi. This review presents their structural diversities and unique biological properties. (2) In the course of our studies on the induced production of new fungal metabolites, the Palauan marine-derived fungus, Trichoderma cf. brevicompactum TPU199, was found to produce the unusual epipolythiodiketopiperazines, gliovirin and pretrichodermamide A. Long-term static fermentation of the strain induced production of a new dipeptide, dithioaspergillazine A, whereas fermentation of the strain with NaCl, NaBr, and NaI produced the Cl and Br derivatives of pretrichodermamide A and a new iodinated derivative, iododithiobrevamide, respectively. Moreover, DMSO-added seawater medium induced the production of diketopiperazine with the unprecedented trithio-bridge, chlorotrithiobrevamide. This fermentation study on the strain as well as the structures of the metabolites obtained are described in this review.

著者

平居 貴生 髙木 三千代 中島 健一 井上 誠

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.6, pp.861-866, 2019-06-01 (Released:2019-06-01)

参考文献数

35

被引用文献数

1

---

Brown adipose tissue is a critical regulator of metabolic health, and contributes to thermogenesis by uncoupling oxidative phosphorylation through the action of mitochondrial uncoupling protein 1 (Ucp1). Recent studies have shown that cold exposure and the stimulation of β3-adrenergic receptors induce the development of brown cell-like “beige” adipocytes in white adipose tissue. Brown and/or beige adipocyte-mediated thermogenesis suppresses high-fat diet-associated obesity. Therefore, the development of brown/beige adipocytes may prevent obesity and metabolic diseases. In the present study, we elucidated whether naturally occurring compounds contribute to regulating the cellular differentiation of brown/beige adipocytes. We screened for the up-regulated expression of Ucp1 during beige adipogenesis using extracts of crude herbal drugs frequently used in Kampo prescriptions (therapeutic drugs in Japanese traditional medicine). This screening revealed that the extract prepared from Citri Unshiu Pericarpium [the peel of Citrus unshiu (Swingle) Marcov.] increased the expression of Ucp1 in beige adipocytes. We also focused on the function of clock genes in regulating brown/beige adipogenesis. Therefore, another aim of the present study was to evaluate naturally occurring compounds that regulate brain and muscle Arnt-like 1 (Bmal1) gene expression. In this review, we focus on naturally occurring compounds that affect regulatory processes in brown/beige adipogenesis, and discuss better preventive strategies for the management of obesity and other metabolic disorders.

著者

木村 健

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.127, no.2, pp.245-256, 2007-02-01 (Released:2007-02-01)

参考文献数

5

被引用文献数

2 3

---

Pharmacist can make an impact on patients' quality of life by providing clinical interventions. These interventions are to be shared with other healthcare professionals and to be utilized to improve quality of care. As an attempt to provide a better care, pharmacists are making patients' record that contains patients' medical history, laboratory values, and conditions. These services are reimbursed by insurance. However, there are some concerns regarding fees for services provided by pharmacists; i.e., fees for patients' instructions are too expensive. One of the problems could be the fact that pharmacist-generated patients' record is not used or utilized by other healthcare personals and it is used only for the purpose of getting reimbursed. Therefore, it is necessary for pharmacists to realize the real purpose of making patients' record and create patients' records that will allow other healthcare professionals to make better therapeutic decisions. Such patients' record should have following characteristics: 1) The record to accomplish the systemic patient care management; 2) The record to share information in the team of medical treatment; 3) The record to define the pharmacist's role in the patient care; 4) The record that is available for the education of the pharmacist's problem-solving abilities; and 5) The record that can be disclosed to the patient and can be a legal basis. Thus, pharmacists should acquire the skills to make higher quality record. In this context, the pharmacy school should cooperate with hospital and community pharmacists, in order to establish education systems for development of these skills.

著者

中山 晋介 寺本 英已

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.10, pp.1345-1354, 2016 (Released:2016-10-01)

参考文献数

20

被引用文献数

1

---

The umami taste amino acid, glutamate acts as a signaling molecule in multiple cellular systems in the body, including the brain and gastrointestinal tract. Therefore, glutamate may affect appetite by modulating gastrointestinal motility as well as through taste perception. In this study, we examined the effect of glutamate on gastric emptying and duodenal motility, by using rapid magnetic resonance imaging (MRI). Ten healthy male volunteers participated in the measurements. Abdominal coronal MR images were successively acquired after ingestion of a liquid meal with and without monosodium L-glutamate (MSG). Image analysis was performed with a homemade segment software, in which respiratory motions were cancelled automatically by minimizing an energy function, thereby allowing participants breathe freely during MRI measurements. In two out of 10 participants, gastric emptying slowed down, while in the remaining eight participants, gastric residual volume decreased to 84% without MSG, and to 73% with MSG after 60 min. The inclusion of MSG enhanced duodenal motility, judging from changes in, 1) the magnitude of the duodenal area, 2) the center of gravity, and 3) the mean velocity of the wall motions. The third parameter most significantly indicated the excitatory effect of MSG on duodenum motility (3-7 fold increase). In conclusion, the present observations of rapid MRI indicate that MSG accelerates gastric emptying by facilitating duodenal motility, at least in healthy subjects with positive responses to MSG. This suggests the possible use of MSG as a prokinetic nutrient for improving the quality of life in hospitalized patients after a clinical assessment.

著者

松木 則夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.116, no.9, pp.710-718, 1996-09-25 (Released:2008-05-30)

参考文献数

31

被引用文献数

7 9

---

In this review, I have attempted to provide an overview of the pathways by which cytotoxic drugs induce emesis. The mechanisms of serotonin 5-HT3 antagonists and new antiemetics are also discussed. Old data especially from the experiments employing area postrema ablation must be re-evaluated because it is likely that the operation has damaged other important nucleus in the brain stem. Therefore, the concept of the chemoreceptor trigger zone and "vomiting center" proposed by Borison et al. in 1950s is questionable. Nausea and vomiting caused by cytotoxic drugs have been a serious problem in anti-cancer therapy and prompted lots of scientists to find the mechanism and to develop antiemetics. Effectiveness of 5-HT3 antagonists were shown in late 1980s, and now they are clinically available. I have investigated their mechanisms using Suncus murinus and proposed that the pathways by which cisplatin, one of most emetogenic drugs, induces emesis are as follows : 1) cisplatin is converted to an active metabolite (s), 2) the metabolite (s) somehow produces oxygen free radicals in the enterochromaffin cells, 3) the free radicals release serotonin, 4) the released serotonin stimulates 5-HT3 receptors located on the vagus afferents, 5) impulses are transmitted to the brain stem, or emetic pattern generator and initiate emetic reflex. Therefore, scavengers of free radicals and antioxidants can be a new type of antiemetic drug.