Blood-pressure lowering, positive chronotropy and inotropy by the Veratrum alkaloids germidine and germerine but negative chronotropy by veratridine in mice.
Germidine and germerine, the Veratrum alkaloids lowered blood pressure accompanied with positive chronotropy and inotropy in mice. Germerine was more potent than germidine in both blood-pressure lowering and positive inotropy, whereas veratridine produced negative chronotropy and positive inotropy. An acyl group (an acetyl or a 2-methylbutyroyl group) at 3-O-R1 position and a 2-methylbutyroyl group at 15-O-R2 position in germine were important to produce the positive inotropy and chronotropy. The presence of a veratroyl group at 3-O-R1 position and a free hydroxyl group at 15-O-R2 position may be essential to produce the negative chronotropy by veratridine. The positive inotropy by germidine and veratridine may be due to TTX-resistant Na+ channel activation.
Department of Chemical Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan. ikukokim@ms.toyama-mpu.ac.jp
I
I
Kimura
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A
Islam
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R
Honda
H
H
Nojima
Y
Y
Tezuka
W
W
Zhao
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D019668:Liliaceae / Q000737:chemistry*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008956:Models, Chemical; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014701:Veratridine / Q000008:administration & dosage / Q000494:pharmacology*; D014704:Veratrum Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010936:Plant Extracts; D014704:Veratrum Alkaloids; C427628:germidine; C427629:germerine; D014701:Veratridine; D011433:Propranolol; D009638:Norepinephrine