著者

中尾 英雄 福島 正美 菅原 眞一

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.93, no.11, pp.1526-1529, 1973-11-25 (Released:2008-05-30)

参考文献数

5

被引用文献数

2 2

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5-Cyano-2-furaldehyde and its derivatives were synthesized and their antimicrobial activities were tested. Neither series of compound possessed significant antimicrobial activity.

著者

植沢 芳広

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.2, pp.185-190, 2018-02-01 (Released:2018-02-01)

参考文献数

14

被引用文献数

4

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Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

著者

片木 宗弘 辰野 道昭 土橋 均

出版者

公益社団法人 日本薬学会

雑誌

衛生化学 (ISSN:0013273X)

巻号頁・発行日

vol.40, no.4, pp.357-364, 1994-08-31 (Released:2008-05-30)

参考文献数

20

被引用文献数

4 4

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The procedure for the determination of the main metabolites of malathion (MA), malaoxon (MO), malathion dicarboxylic acid (DCA), malathion α-, β-monocarboxylic acid (α-, β-MCA), desmethyl malathion (DM-MA), in addition to unchanged MA was investigated using positive-ion mode thermospray liquid chromatography-mass spectrometry (TSP-LC/MS). Following the solid-phase extraction of the sample at pH 2 using Sep-Pak C18 cartridge with methanol as eluent, the extract was analyzed on TSP-LC/MS. LC analyses were performed on C18-bonded phase using methanol-100 mM ammonium acetate (60 : 40 v/v, pH 3.65 with trifluoro acetic acid) as eluent at a flow rate of 1.0 ml/min. Every mass spectrum of MA and its metabolites provided both the protonated molecular ion [M+H]+ and the ammonium adduct ion [M+NH4]+. By the solid-phase extraction, they were recovered relatively well, and the detection limits were ranged from 0.2 μg/ml to 2.5 μg/ml by scan mode, ranged from 5 ng/ml to 200 ng/ml by selected ion monitering (SIM) mode. In the urine sample, the coefficients of variations for the prepared method by SIM mode were ranged from 3.3% to 7.2% at 500 ng/ml level of each metabolite. For a blood sample of a female, who had committed suicide by taking MA, TSP-LC/MS analysis were attemped following the prepared method, the metabolites such as α-MCA were detected, and it was possible to prove that she had taken MA.

著者

関口 富美子

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.125, no.6, pp.491-498, 2005 (Released:2005-06-01)

参考文献数

56

被引用文献数

5 5

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Protease-activated receptors (PARs), a family of G-protein-coupled seven-transmembrane-domain receptors, are activated by proteolytic unmasking of the N-terminal cryptic tethered ligand by certain serine proteases. Among four PAR family members cloned to date, PAR-1, PAR-2, and PAR-4 can also be activated through a non-enzymatic mechanism, which is achieved by direct binding of exogenously applied synthetic peptides based on the tethered ligand sequence, known as PARs-activating peptides, to the body of the receptor. Various peptide mimetics have been synthesized as agonists for PARs with improved potency, selectivity, and stability. Some peptide mimetics and/or nonpeptide compounds have also been developed as antagonists for PAR-1 and PAR-4. PARs are widely distributed in the mammalian body, especially throughout the alimentary systems, and play various roles in physiological/pathophysiological conditions, i.e., modulation of salivary, gastric, or pancreatic glandular exocrine secretion, gastrointestinal smooth muscle motility, gastric mucosal cytoprotection, suppression/facilitation of visceral pain and inflammation, etc. Thus PARs are now considered novel therapeutic targets, and development of selective agonists and/or antagonists for PARs might provide a novel strategy for the treatment of various diseases that are resistant to current therapeutics.

著者

甘露寺 泰雄

出版者

公益社団法人 日本薬学会

雑誌

衛生化学 (ISSN:0013273X)

巻号頁・発行日

vol.18, no.2, pp.90-95, 1972-04-30 (Released:2008-05-30)

参考文献数

15

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Intrusion of sea water into thermal water was generally observed in thermal springs in coastal area at Asamushi Spa. It has been known that the chemical composition of sea water changes considerably in the process of the intrusion. Behavior of some components such as sodium, potassium, calcium, and magnesium ions, in the process of the intrusion is discussed by the analysis of the mixing ratio of sea water into thermal water. 1. The mixing ratios of eight thermal springs of high salinity are approximately calculated by the following equation, provided that a thermal water of high salinity is a mixture of sea water and original thermal water. [numerical formula] where S is the content of Na, K, Ca, Mg, Cl, SO4, or HCO3, in sea water, H, the content of above components in original thermal water, and A, the values of chemical analyses of thermal water. 2. The mixing ratio of sea water shows various values according to components in one spring water. This is the reason why the behavior of each component is different in the process of the intrusion of sea water. The ratio calculated from Ca is the highest, and the ratio from K or HCO3 the lowest, and the order of the ratios is generally Ca>Cl>Na>Mg>K. 3. It is assumed that sodium, potassium, and magnesium ions in sea water decrease by the absorption on the minerals by passing through the aquiferous strata, and calcium ion increases by the ion-exchange effect caused by the absorption of sodium, potassium, and magnesium ions.

著者

南雲 康行

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.50, no.11, pp.1146-1146, 2014 (Released:2016-09-30)

参考文献数

3

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神経細胞の正常な機能発現には,神経細胞内外におけるCl-の適切な濃度勾配形成と維持が不可欠となる.正常な神経細胞内のCl-は,細胞外よりも低濃度に維持され,この状態が正常に保たれることで,GABAやグリシンによる細胞内へのCl-流入の適切な方向付けと即時的な強い抑制作用を発揮する.成熟神経細胞における細胞内Cl-濃度は,K+―Cl-共輸送体(K+―Cl- cotransporter:KCC2)によって調節される.神経細胞特異的に発現するKCC2は,Cl-の細胞外排出を担うイオン輸送体であり,これによって細胞内のCl-を低濃度に保つことができる.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Coull J. A. et al., Nature, 424, 938-942 (2003).2) Huberfeld G. et al., J. Neurosci., 27, 9866-9873 (2007).3) Gagnon M. et al., Nat. Med., 19, 1524-1528 (2013).

著者

藤井 節郎 奥田 拓道 赤沢 明 安田 行寛 川口 安郎 福永 育史 西川 栄郎

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.95, no.6, pp.732-740, 1975-06-25 (Released:2008-05-30)

参考文献数

13

被引用文献数

4 5

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In order to investigate the fate of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) in comparison with that of 5-fluorouracil tritiated FT-207 (3H-FT-207) and 5-fluovouracil (3H-5-fluorouracil)were administered from the rectum in normal and AH-130 tumor-bearing rats, and rapid absorption of 3H-FT-207 or 3H-5-fluorouracil, was observed. Blood level of radioactivity after rectal administration of 3H-FT-207 was higher and more continuous than that of 3H-5-fluorouracil. Although the radioactivity after rectal administration of 3H-FT-207 and 3H-5-fluovouracil was widely distributed in the various tissues of the animal with or without tumor, the highest concentration of the radioactivity was observed in the kidneys, and higher in tumor. The radioactivity in lymphatic gland reached a maximum level within 2-4 hr after the rectal administration of 3H-FT-207 and declined very slowly. The urinary excretion of radioactivity within 24 hr was about 30% of the administered dose of 3H-FT-207. More than 85% of the excreted radioactivity accounted for FT-207 and its metabolite, α-fluoro-β-alanine. Other metabolites such as 5-fluorouracil, α-fluoro-β-ureidopropionic acid and tritiated water were detected in small amounts in rat urine. The radioactivity in blood and tumor, 4 hr after rectal administration of 3H-FT-207, was found to represent FT-207. However, the radioactivity in liver was due to the presence of α-fluoro-β-alanine. About 90% radioactivity in lymphatic gland within 2-6 hr after rectal administration of 3H-FT-207 was detected as FT-207.

著者

才川 勇 高井 明 中島 良文 吉田 長作 保田 隆 清水 悦郎 酒井 広志 滝 秀雄 田井 賢 高下 寛

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.97, no.10, pp.1071-1081, 1977-10-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

5 3

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Metabolism of 6-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido) phenylacetamido] penicillanic acid (T-1220), a new β-lactam antibiotic, was studied in vivo and in vitro. Only unchanged T-1220 was detected by bioautography in urine of human, monkeys, dogs, rats, and mice receiving T-1220 intramuscularly. When 14C-labeled T-1220 was administered to rats, most of the radioactive product was excreted unchanged in the urine, but two metabolites were detected in a minute amount by autoradiography. These metabolites were identified as 14C-labeled α-{3-[2-(N-ethyl-N-oxaloamino) ethyl] ureido}-benzylpenicillin (14C-T-1220A) and 14C-labeled α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido) benzylpenicilloic acid (14C-T-1220B) by thin-layer chromatography, electrophoresis, and high-pressure liquid chromatography. Metabolism of 14C-T-1220 and its mechanism were studied by using high-pressure liquid chromatography for the separation and radioactive measurement for the determination. In the case of the intramuscular administration of 14C-T-1220 to rats, about 92% of the radioactivity was excreted unchanged in urine and bile, but about 94% of the radioactivity in the feces was 14C-T-1220B. The same results were found in rats pretreated with SKF-525A and phenobarbital. In situ studies showed that 14C-T-1220 changed to 14C-T-1220B in the intestinal tracts, and in vitro studies showed that 14C-T-1220 changed to 14C-T-1220B in fecal homogenate. From these results, it seemed that 14C-T-1220 was changed to 14C-T-1220B by β-lactamase produced from intestinal flora.

著者

スレス アワレ

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.54, no.5, pp.455-455, 2018 (Released:2018-05-01)

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母国ネパ-ルの高校生時代から化学に情熱があり,薬用植物から創薬の夢があったため,日本唯一の和漢薬研究所に留学にきた.言葉・異文化などに慣れるまで時間が掛かり,留学生時代は大変だった.博士課程修了後,ポスドク研究員・助教を経って,テニュアトラック特命教員の国際公募の機に応募・合格し,その後頑張って今の職に就いた.その旅の中結婚し子供に恵まれ,学術界以外の様々な場面より日本の伝統文化や特徴をさらに実感・理解できた.日本人の丁寧さおよび伝統の守りに心を打たれるが,日本人の曖昧な言い回しが苦手である.

著者

川口 安郎 中村 芳正 佐藤 俊幸 武田 節夫 丸中 照義 藤井 節郎

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.98, no.4, pp.525-536, 1978-04-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

5 8

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After oral administration of 5-fluoro-1, 3-bis (tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FD-1), the level of 5-fluoro-2, 4-pyrimidinedione (5-FU) was 5 to 7 times higher in the plasma and normal tissues and 8 to 12 times in tumor tissue than after administration of 5-fluoro-1-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FT). Moreover, these levels were maintained longer than after administration of FT. In tumor tissue, the concentration of 5-FU was still as high as 1.42 μg/g 12 hr after administration of FD-1. FD-1 was degraded to 5-fluoro-3-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (3-FT) by liver microsomal drug-metabolizing enzymes in vitro and to FT spontaneously. Subsequently, FT was converted enzymically to the active substance, 5-FU, and 3-FT changed to 5-FU spontaneously. Conversion of FD-1 to 5-FU via 3-FT was greater than via FT. It is concluded that a large amount of 5-FU formed after administration of FD-1 is formed via 3-FT. γ-Hydroxybutyric acid was found to be formed in vivo and in vitro from the tetrahydrofuranyl group of FD-1.

著者

東田 道久

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア

巻号頁・発行日

vol.53, no.1, pp.7_1-7_1, 2017

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街ではみみにふたをして歩いている人をよく見かける。あれはよろしくない。みみは危険察知アンテナとして最も感度の良い器官であり、それにふたをすると危険に反応できない。著者は最近とんでもないスピーカーを買い、静寂を目指して引いていく音の響きの美しさにめざめた。そこには「精度と純度」がある。人生の引き際にもその美学を反映させたいが、そのためには種々の意見に純粋な気持ちでみみを傾け、脳を刺激し続けることが大切な気がする。

著者

本山 桜

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.52, no.9, pp.872-873, 2016 (Released:2016-09-02)

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効能効果:気分不快,口臭,二日酔い,宿酔,胸つかえ,悪心嘔吐,溜飲,めまい,暑気あたり,乗り物酔い成分分量:【有効成分】阿仙薬,甘草末,カンゾウ粗エキス末,桂皮,丁字,益智,縮砂,木香,生姜,茴香,l-メントール,桂皮油,丁字油,ペパーミント油.【その他の成分】甘茶,トウモロコシデンプン,バレイショデンプン,中鎖脂肪酸トリグリセリド,d-ボルネオール,香料,銀箔,アラビアゴム末.用法用量:大人(15才以上)1回10粒,(11才以上15才未満)1回7粒,(8才以上11才未満)1回5粒,(5才以上8才未満)1回3粒,1日10回まで適宜服用(上記は現在販売している「仁丹」のものを記載).

著者

並木 徳之

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.135, no.2, pp.237-243, 2015 (Released:2015-02-01)

参考文献数

5

被引用文献数

2 9

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Orally disintegrating tablets (ODTs) are currently widely used in drug therapy and are clinically attractive, because they are suitable for administration to patients with dysphagia and improve adherence, both of which increase the possibility of achieving the expected therapeutic effect. These properties of ODTs, which increase treatment effectiveness, are termed their “clinical functionality”, and ODTs with a high clinical functionality are required to meet the increasing need for these tablets. For example, there is a need for development of a clinically effective ODT with superior disintegrating properties while maintaining high tablet strength, bioequivalence with normal tablets while masking the bitterness with a fine particle coating, and a disintegration mechanism while maintaining moisture resistance and good storage quality. Thus, next-generation ODTs that overcome these conflicting properties, “trade-offs”, will be developed, using innovative formulation research technology. In this symposium, we will discuss a next-generation OD formulation known as PLETAAL OD, a high-dose antiplatelet agent, and will present the results of validation tests performed in our laboratory pertaining to high tablet strength, superior disintegration property, high wicking capacity, and storage stability with high moisture resistance. We will also introduce a second-generation antihistamine ALLELOCK OD and discuss its high clinical functionality achieved by masking the bitterness and obtaining bioequivalence with normal tablets by using granules while maintaining high tablet strength with EXLUB and SOLBLET technology.

著者

斉藤 文彦

出版者

公益社団法人 日本薬学会

雑誌

MEDCHEM NEWS (ISSN:24328618)

巻号頁・発行日

vol.26, no.4, pp.216-220, 2016-11-01 (Released:2018-03-15)

参考文献数

1

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National Medicinal Chemistry Symposium(NMCS)は、ACS Division of Medicinal Chemistry主催で1948年より隔年で開催されている。今回の第35回シンポジウム(NMCS2016)は、2016年6月26~29日までの4日間、イリノイ州シカゴで開催された。29の国・地域から約350名の参加があり、受賞・招待講演である口頭発表が26演題、ポスター発表が109演題であった。1日目は「DMPKに関する最近の話題」と「受賞講演」、2日目は「転写因子ターゲット」、「エピジェネティック メカニズム」と「ポスターセッション」。3日目は「神経変性疾患に対する治療の最近の進歩」、4日目は「オープンイノベーション」と「アンドラッガブルからドラッガブルへ」についての講演であった。本レポートでは口頭発表のなかからいくつかの演題について報告する。

著者

小村 弘 河原 亥一郎 茂本 友貴枝 松田 健一 阿野 理恵子 村山 洋子 森脇 俊哉 吉田 長弘

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.125, no.1, pp.121-130, 2005-01-01 (Released:2005-01-01)

参考文献数

27

被引用文献数

3 5

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The application of combinatorial chemistry and high-throughput screening to biological targets has led to efficient identification of lead compounds in wide therapeutic areas. However, the physicochemical properties of some lead compounds are lipophilic with low water soluble. Since these parameters determine in vivo absorption, we established robust screening methods for solubility and Caco-2 membrane permeability which are applicable to our screening strategy based on the structure-pharmacokinetic parameter relationship (SPR). Of test compounds with different core structures, turbidimetric solubility and apparent solubility as determined by HPLC-UV analysis after dilution of aqueous media from DMSO stock solution was overestimated in comparison with the corresponding thermodynamic solubility obtained using a traditional shake-flask method. A new powder-dissolution method providing thermodynamic solubility similar to that in the traditional method was developed using 96-well plates for equilibrium dialysis. The throughput of the method was the almost the same as that using the apparent solubility method. In a conventional Caco-2 assay, membrane permeability (Papp) of some lipophilic compounds was underestimated due to low solubility in the apical site and adhesion to the device, resulting in a poor relationship between the in vivo absorption fraction and the Papp values. The addition of 0.1% Gelucire 44/14 into the apical site and 4% bovine serum albumin into the basolateral site improved the relationship. These newly developed methods are therefore useful to optimize lead compounds with less water solubility and high lipophilicity on the basis of SPR.

著者

山岸 三郎 小山 泰正 深草 佑一 興村 伸夫 大石 洵一 浜道 則光 新井 正

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.91, no.3, pp.351-357, 1971-03-25 (Released:2008-05-30)

参考文献数

24

被引用文献数

14 21

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The metabolites of Streptomyces luteoreticuli KATOH et ARAI were investigated. Four new compounds, luteoreticulin, (V), C19H19O5N, luteothin, (VI), C22H25O5N, metabolite X, (X), C15H12O3N2, and metabolite XI, (XI), C15H14O3N2, were isolated from the acetone extract of the mycelial cake. 1-Methoxyphenazine (VII) and methyl phenazine-1-carboxylate (IX), which were first isolated from natural origin, were obtained in addition to aureothricin (I), thiolutin (II), aureothin (IV), and 1, 6-dimethoxyphenazine (VIII). The other two metabolites (III and XII) were also isolated but not identified.

著者

高倉 喜信

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.7, pp.519-532, 1996-07-25 (Released:2008-05-30)

参考文献数

59

被引用文献数

5 7

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With a rapid progress in biotechnology, a variety of endogenous macromolecular substances have become a novel class of therapeutic agents. This review will focus on the development of delivery systems for macromolecular drugs. Current status and future perspectives in this research field are reviewed mainly based on the results obtained in our laboratory. First of all, we studied pharmacokinetic characteristics of macromolecules in relation to their physicochemical properties such as molecular weight and electric charge. Based on this information, we first developed macromolecular prodrugs as a delivery system for low molecular weight drugs. An antitumor antibiotic, mitomycin C (MMC) were covalently conjugated with dextran and various types of macromolecular prodrug of MMC were developed for tumor targeting. Secondly, delivery systems for protein drugs such as soybean trypsin inhibitor, uricase, and recombinant superoxide dismutase (SOD) were developed. In particular, successful targeting of SOD to the liver, kidney and blood circulation was achieved by chemical modification of the protein drug. Finally, we have been trying to develop delivery systems for nucleic acid drugs involving antisense oligonucleotides and plasmid DNA. Prior to the development of delivery systems, we found that the pharmacokinetics of the nucleic acid drugs are decided by their physicochemical properties as polyanions even if these materials contain genetic information. Several approaches were tested to control the in vivo behavior of the oligonucleotides and plasmid DNA based on the finding. Thus, we have established the strategy for rational design of delivery systems for various types of macromolecular drugs based on the pharmacokinetic considerations. This methodology can be a formidable tool for the development of clinically applicable macromolecular drugs.

著者

生塩 孝則 遠藤 寛二 山本 恵司

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.11, pp.866-875, 1996-11-25 (Released:2008-05-30)

参考文献数

21

被引用文献数

3 4

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The physicochemical properties of the enantiomer and racemates of suplatast tosilate (ST) were investigated by means of infrared spectroscopy, solid-state 13C CP/MAS NMR spectroscopy, thermal analysis, and X-ray diffraction analysis, and by measuring the solubility and hygroscopy. The infrared and NMR spectra and X-ray diffraction pattern of the enantiomer were distinctly different from those of the racemate. The melting point of the enantiomer was lower than that of the racemate by 5°C, while the solubility of the enantiomer was 1.3 times higher than that of the racemate. The hygroscopic rate of the enantiomer was greater than that of the racemate. These results suggested that ST was classified into a racemic compound crystal. Furthermore, by comparing the relative peak intensity ratios on X-ray diffraction patterns of crystals with various optical purities prepared by recrystallization, it was found that a mixture of racemic compound crystals and either of racemic mixture crystals or racemic solid solutions was obtained by recrystallization of ST in the content of 0 to 64%ee, while the recrystallization of ST in the content of more than 64%ee led to the formation of racemic mixture crystals or racemic solid solutions.

著者

太田 和子

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.87, no.4, pp.444-450, 1967-04-25 (Released:2008-05-30)

参考文献数

14

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Some considerations were made on the action mechanism of 2-naphthalenealkylamines, with O-7 carbons in the alkyl chain, and their N-alkyl- or N-aralkyl-N-methyl derivatives by measuring their kinetic activity, applying Fergusson's rule to their pharmacological activity. It was thereby found that the atropine-like and antihistamine activities of these compounds are specific action and contribution of the physicochemical properties of the base is very small. On the other hand, their papaverine-like action in the intestine is not so specific like atropine-like activity although in a strong base like the compounds of this series, a certain contribution of the cation is expected. Local anesthetic action was found to be non-specific, being dependent on the physicochemical properties of the non-ionic base or neutral molecule. This fact was further endorsed by the relationship between surface anesthetic action and pH.

著者

太田 和子

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.86, no.9, pp.756-759, 1966-09-25 (Released:2008-05-30)

参考文献数

5

被引用文献数

1

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Local anesthetic action of recently synthesized 2-naphthalenealkylamines was tested. Surface anesthetic action was tested by the corneal reflex of a guinea pig and N-alkyl-N-methyl-2-naphthaleneethyl (or propyl) amines (XIb∼f, XIIb∼f) all showed activites stronger than that of procaine, and N-methyl-N-pentyl-2-naphtha1eneethylamine (XIf) was especially strong, the potency being 16 times that of procaine. The activity decreased when the compounds of this series were derived to methiodide, and only the N-butyl and N-pentyl compounds showed a weak activity. This fact seems to indicate the possibility that the base of a compound takes part in appearance of the activity. Primary amines (IIa to Xa) generally had strong irritant psoperty N, N-Dimethyl derivatives (IIb to Xb) showed the activity only when the number of carbon atoms in the side chain was 2 (IVb) or 3 (Vb), and all higher homologs had strong toxicity necrosis. Conduction anesthetic activity was examined with frog sciatic nerve in compounds of XI and XII series and their potency was compared with that of procaine. Approximately similar structure-activity relationship as in the case of surface anesthetic activity was found.