Effects of Aconitum Alkaloid Kobusine and Pseudokobusine Derivatives on Cutaneous Blood Flow in Mice; II
| Autor: | Norio Kawahara, Koji Wada, Eiichi Fujihira, Takao Mori, Satoshi Ishizuki |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Bridged-Ring Compounds
Male Stereochemistry Vasodilator Agents Pharmaceutical Science Hemodynamics Vasodilation Ranunculaceae Pharmacognosy Pharmacology Magnoliopsida Mice Animals Polycyclic Compounds Aconitum Skin Mice Inbred ICR Esterification biology Chemistry Alkaloid Biological activity General Medicine Phenanthrenes biology.organism_classification Dose–response relationship Regional Blood Flow Injections Intravenous Diterpenes |
| Zdroj: | Biological and Pharmaceutical Bulletin. 23:607-615 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.23.607 |
| Popis: | Aconitum alkaloids of the C20-diterpenoid type, kobusine (1) and pseudokobusine (2), and their acetyl, benzoyl, propionyl or cinnamoyl derivatives are examined for their peripheral vaso-activities by laser-flowmetrical measurement of the cutaneous blood flow in the hind foot of mice after intravenous administration. A dose-relationship of maximally increased blood flow after the administration of either of the Aconitum alkaloids existed. Kobusine 15-acetate (4), 11-benzoate (6) and 15-benzoate (7) were significantly effective at a low dose of 1 mg/kg, whereas the other kobusine derivatives were all inactive. Alkaloid 2, alone, and the 11-acetate (14), 15-acetate (15), 15-propionate (22) and 15-cinnamoate (25) were all active at 1 mg/kg and the effect of 14 at 5 mg/kg was remarkable. The activity of 2 was abolished by esterification of the hydroxyl group at C-6. Alkaloid 15 at 5 mg/kg showed a pattern of time course of blood flow in which the increase was rapidly replaced with a decrease below the basal flow, probably suggesting the effect of excessive doses. Conclusively, it is considered that the hydroxyl groups of alkaloids, especially a free OH group of 2 at C-6, are important for action on the peripheral vasculature leading to dilatation, and these results indicated that esterification of the hydroxyl group at C-15 with either acetate or benzoate may contribute to enhancement of the activity of the parent alkaloids. |
| Databáze: | OpenAIRE |
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