著者

山本 郁男 吉村 英敏

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.28, no.5, pp.233-248, 1982-10-30 (Released:2008-05-30)

参考文献数

117

被引用文献数

2 1

---

This review is concerned primarily with our recent papers which have been published or presented since 1978. Especially, metabolic conversion of Δ8-THC to Δ8-THC-11-oic acid and to 8α, 9α-epoxyhexahydrocannabinol (8α, 9α-EHHC) and their pharmacological implications are described. Liver microsomes catalyze formation of 11-OH-Δ8-THC from Δ8-THC, 11-oxo-Δ8-THC from 11-OH-Δ8-THC, and 8α, 9α-EHHC from Δ8-THC. The involvement of cytochrome P-450 in these reactions were suggested in vivo as well as in vitro. 11-OH-Δ8-THC was detected and determined as a metabolite in vivo of Δ8-THC in the liver and brain of mice. 11-OH-Δ8-THC, when administered to mice, showed higher distribution in the brain as compared with Δ8-THC. Pharmacological activities of 11-OH-Δ8-THC, 11-oxo-Δ8-THC, Δ8-THC-11-oic acid, 8α, 9α-EHHC, 8β, 9β-EHHC, 9α, 10α-EHHC and 8β, 9α-di OH-HHC were compared with that of Δ8-THC using mice. Pharmacological effect of 11-OH-Δ8-THC, 11-oxo-Δ8-THC, 8β, 9β-EHHC and 9α, 10α-EHHC were more potent than that of Δ8-THC in the cataleptogenic, hypothermic, pentobarbital-induced sleep prolonging, and anticonvulsant effects. Daily administration of 11-OH-Δ8-THC or 11-oxo-Δ8-THC as well as Δ8-THC quickly induced tolerance to their hypothermic and pentobarbital-induced sleep-prolonging effects. The LD50s of 11-OH-Δ8-THC, 11-oxo-Δ8-THC and Δ8-THC-11-oic acid are larger than that of Δ8-THC.

著者

松永 民秀 渡辺 和人 吉村 英敏 山本 郁男

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.118, no.9, pp.408-414, 1998-09-01

---

△^9-Tetrahydrocannabinol (△^9-THC), cannabinol, cannabidiol and cannabichromene were detected in commercially available cannabis seeds by silica gel TLC and gas chromatography. These cannabinoids existed in rather high content (0.10-2.02mg/100g of seeds) in the feed for birds, especially bracts (82.3-441mg/100g). When the suspension prepared from the benzene washing solution of cannabis seeds, BenW, was administered at a dose of 3mg/kg corresponding to △^9-THC into a mouse, i.v., BenW caused hypothermia, catalepsy, pentobarbital-induced sleep prolongation and suppression of locomotor activity. These pharmacological activities of BenW were significantly higher than those of △^9-THC (3mg/kg, i.v.). These results may indicate the necessity to reconsider the present regulations on marihuana.

著者

荒牧 繁一郎 富安 温子 吉村 英敏 塚元 久雄

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.16, no.5, pp.822-826, 1968-05-25 (Released:2008-03-31)

被引用文献数

67 85

---

A new solvent system benzene-n-hexane-diethylamine (25 : 10 : 1), was found to show a good separation of cannabidiol, tetrahydrocannabinol and cannabinol in hemp resin by thin-layer chromatography, in which Rf-values of three constituents were 0.45, 0.35 and 0.25, respectively. Furthermore, the same solvent system was successfully applied to silica gel column chromatography for isolation of three constituents of hemp resin. Using cocaine hydrochloride as an internal standard of gas chromatography, relative retention times of cannabidiol, tetrahydrocannabinol and cannabinol were calculated to be 1.76, 2.34 and 2.88, respectively. Six kinds of hemps grown in India, U.S.A. and Japan, were quantitatively analyzed using gas chromatography, and against a common opinion, Japanese hemps were found to contain considerable amounts of tetrahydrocannabinol, a physiologically active constituent.

著者

小栗 一太 吉村 英敏

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.32, no.6, pp.413-426, 1986-12-31 (Released:2008-05-30)

参考文献数

105

被引用文献数

1 1

---

Recent progress of forensic toxicology of morphine and heroin, and of the boundary area was reviewed. Topics included in this review were 1) opioid peptides, 2) opioid receptors, 3) endogenous morphine, 4) metabolism of morphine : glucuronidation, sulfate conjugation, N-demethylation and dehydrogenation, 5) pharmacological activity of morphine conjugates, 6) metabolism of heroin, 7) analytical methods of morphine and heroin for forensic toxicological purpose.

著者

塚元 久雄 吉村 英敏

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.15, no.4, pp.213-218, 1969-08-30 (Released:2008-05-30)

参考文献数

10

著者

吉村 英敏 山本 弘明 佐伯 清太郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.21, no.10, pp.2231-2236, 1973-10-25 (Released:2008-03-31)

被引用文献数

22 23

---

In order to understand the toxic nature of Kanechlor-400 (KC-400, a commercial preparation of polychlorinated biphenyls) and establish the treatment of the patients of this KC-400 intoxication (so-called Yusho), metabolic fate of 2, 4, 3', 4'-tetrachlorobiphenyl (2, 4, 3', 4'-TCB), a major component of KC-400, was investigated using rats. It was found that at least four metabolites having phenolic nature were excreted exclusively into the feces together with a large amount of unchanged 2, 4, 3', 4'-TCB. Among these, a major metabolite (M-A2), mp 155-156°, and a minor metabolite (M-A1), mp 92-98°, were isolated from the feces and characterized to be monohydroxylated TCB by ultraviolet, infrared, nuclear magnetic resonance, and mass spectral analyses. After 2, 4, 3', 4'-TCB was orally administered at a single dose of 25 mg/body to the rat, a little less than one half of the dose was excreted as unchanged 2, 4, 3', 4'-TCB during 12 days, most of which were eliminated in the first day. The excretion of major metabolite reached maximum at the second day, and total M-A2 was accounted for about 10% of dose during 12 days. Both 2, 4, 3', 4'-TCB and its major metabolite were still excreted in a small but significant amount on 12th day.

著者

吉村 英敏 小沢 直記 佐伯 清太郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.26, no.4, pp.1215-1221, 1978-04-25 (Released:2008-03-31)

被引用文献数

53 65

---

The inductive effect of Kanechlor 400 (KC-400), the Japanese polychlorinated biphenyl (PCB) preparation containing 48% chlorine, and several individual PCB isomers on the hepatic microsomal enzymes of rats was investigated. Pretreatment with KC-400 increased significantly the activity of microsomal aminopyrine (AM) demethylase, aniline (AN) hydroxylase and NADPH-cytochrome c reductase, and the content of cytochromes P-450 and b5 just like phenobarbital (PB)-pretreatment. However, it afforded the CO-difference spectrum revealing the peak at 448 nm same as pretreatment with 3-methylcholanthrene (MC). The inhibitory effect of SKF 525-A and 7, 8-benzoflavone on AM demethylation and AN hydroxylation, respectively, in KC-400-induced microsomes also resembled that in microsomes induced by PB plus MC. Further studies using individual PCBs indicated that these compounds were divided into two groups ; namely, 4, 4'-dichlorobiphenyl (DCB), 2, 5, 2', 5'-and 2, 4, 3', 4'-tetrachlorobiphenyl (TCB) were categorized as PB-type, whereas the other group including 3, 4, 3', 4'-TCB, 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) and 3, 4, 5, 3', 4', 5'-hexachlorobiphenyl (HCB) was categorized as MC-type inducers. Decachlorobiphenyl, the completely chlorinated biphenyl derivative, was found to belong to PB-type. These conclusions were further supported by a spectral study with hexobarbital, which induced type I spectral changes with microsomes from control and 2, 4, 3', 4'-TCB-treated rats, and caused modified type II spectral change with microsomes from 3, 4, 5, 3', 4'-PenCB-treated rats. Considering these results with individual PCBs, it can be assumed that chlorination of both of the para-(4, 4') and two of the meta-positions (3, 3' or 5, 5') of biphenyl is a minimum requirement for the structure to induce cytochrome P-448.