In Vitro Metabolic Formation of a New Metabolite, 6.BETA.-Hydroxymethyl.DELTA.9-tetrahydrocannabinol from Cannabidiol through an Epoxide Intermediate and Its Pharmacological Effects on Mice.
この論文をさがす
抄録
The oxidative metabolism of cannabidiol (CBD) at the 8, 9-double bond was examined. 8R, 9-Epoxy-CBD was identified by GC-MS as a new metabolite of CBD produced by hepatic microsomal fractions of guinea pigs, rats and mice. The reaction required NADPH as a cofactor and molecular oxygen. The optimal pH for the reaction was 7.4-8.0. The 8R, 9-epoxy-CBD forming activity was highest in guinea pigs, followed by mice and rats in the presence of 3, 3, 3-trichloropropene-1, 2-oxide (TCPO), an inhibitor of epoxide hydrolase. The activity was significantly suppressed by SKF 525-A, α-naphthoflavone, metyrapone and carbon monoxide. 8R, 9-Epoxy-CBD was further converted to 6β-hydroxymethyl-Δ9-tetrahydrocannabinol (6β-CH2OH-Δ9-THC) and 8, 9-dihydro-8, 9-dihydroxy-CBD by hepatic microsomes of guinea pigs, rats and mice. Microsomal formation of 6β-CH2OH-Δ9-THC was markedly increased in the presence of TCPO with a concomitant decrease in the formation of 8, 9-dihydro-8, 9-dihydroxy-CBD in all animal species examined. Furthermore, 6β-CH2OH-Δ9-THC was also identified as a new metabolite of CBD produced by hapatic microsomes of guinea pigs. 6β-CH2OH-Δ9-THC exhibited THC-like pharmacological effects, catalepsy, analgesia, pentobarbital-induced sleep prolongation and hypothermia in mice, although these effects were less marked than those of Δ9-THC. This study presents the first example of the biotransformation of CBD to a Δ9-THC derivative which exhibits some pharmacological effects.
収録刊行物
-
- Biological & Pharmaceutical Bulletin
-
Biological & Pharmaceutical Bulletin 16 (10), 1008-1013, 1993
公益社団法人 日本薬学会
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1390282679599856256
-
- NII論文ID
- 110003640176
-
- NII書誌ID
- AA10885497
-
- ISSN
- 13475215
- 09186158
-
- PubMed
- 8287029
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- Crossref
- PubMed
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可