Effects of Aconitum alkaloid kobusine and pseudokobusine derivatives on cutaneous blood flow in mice; II.
Aconitum alkaloids of the C20-diterpenoid type, kobusine (1) and pseudokobusine (2), their anisoyl, veratroyl, p-nitrobenzoyl, nicotinoyl or pivaloyl derivatives, and dehydrokobusine and N,6-seco-6-dehydropseudokobusine derivatives were examined for their peripheral vaso-activities by laser-flowmetrical measurement of the cutaneous blood flow in the hind foot of mice after intravenous administration. Kobusine 15-anisoate (4), 11-veratroate (5), 15-veratroate (6), 11-pivaloate (9) and 15-pivaloate (10) were significantly effective at a low dose of 0.5 or 0.05 mg/kg. Pseudokobusine derivatives were all active at 1, 0.5 or 0.05 mg/kg, and the effects of pseudokobusine 15-anisoate (13), 15-veratroate (16) and 15-p-nitrobenzoate (19) at 0.1 mg/kg were remarkable. Yesoline (26) and alkaloid (28) were significantly effective at a low dose of 1 mg/kg, whereas yesonine (25) and N-acetyl-N,6-seco-6-dehydropseudokobusine (27) were inactive. Dehydrokobusine derivatives (29, 30) were significantly effective at a low dose of 0.5 or 0.1 mg/kg. It is thought 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 the results indicated that esterification of the hydroxyl group at C-15 with either anisoate, veratroate orp-nitrobenzoate may contribute to enhancement of the activity of the parent alkaloids.
Wada
K
K
Hokkaido College of Pharmacy, Otaru, Japan. kowada@hokuyakudai.ac.jp
Ishizuki
S
S
Mori
T
T
Fujihira
E
E
Kawahara
N
N
D000818:Animals; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes; D004951:Esterification; D007275:Injections, Intravenous; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D001952:Bridged-Ring Compounds; D004224:Diterpenes; D010616:Phenanthrenes; D011083:Polycyclic Compounds; D014665:Vasodilator Agents; C111428:kobusine; C111430:pseudokobusine