来自马钱子属植物三叉神经马钱子根的单萜生物碱坎特莱因及其解痉特性。

The monoterpene alkaloid cantleyine from Strychnos trinervis root and its spasmolytic properties.

作者信息

da Silva T M, da Silva B A, Mukherjee R

机构信息

Laboratório de Tecnologia Farmaceutica, Universidade Federal da Paraíba, Brazil.

出版信息

Phytomedicine. 1999 Jul;6(3):169-76. doi: 10.1016/S0944-7113(99)80005-1.

DOI:10.1016/S0944-7113(99)80005-1

PMID:10439481

Abstract

Cantleyine, a monoterpene alkaloid isolated from the root bark of Strychnos trinervis, was submitted to a broad spectrum pharmacological screening, in which the principal effect observed was a nonspecific relaxation of isolated smooth muscles. Cantleyine relaxed (IC50 2.1 x 10(-4) M) the guinea-pig trachea, pre-contracted by carbachol and antagonized in a nonspecific manner; carbachol (IC50 2.1 x 10(-4) M) and histamine (IC50 1.4 x 10(-4) M) induced contractions in the guinea-pig ileum; and phenylephrine (IC50 3.8 x 10(-4) M) responses in the rat aorta. Cantleyine antagonized (pD'2, 3.82) cumulative concentration response curves to histamine in the ileum in a noncompetitive, reversible (slope, 4.84) and concentration dependent manner. The tonic contractions induced by histamine and KCl were also inhibited in a concentration-dependent and reversible manner (IC50 7.2 x 10(-5) and 1.8 x 10(-4) M, respectively), suggesting that cantleyine should be acting on voltage-dependent Ca2+ channels. This hypothesis was confirmed by the observation that cantleyine inhibited (pD'2, 3.35), in a concentration dependent manner, the CaCl2 induced contraction in depolarizing medium. These results suggest that cantleyine produces nonspecific spasmolytic effects in smooth muscle and that in guinea-pig ileum this effect is, in part, due to the inhibition of Ca+2 influx through voltage-dependent Ca2+ channels.

摘要

坎特利因是从马钱子的根皮中分离出的一种单萜生物碱，对其进行了广泛的药理学筛选，观察到的主要作用是对离体平滑肌的非特异性松弛。坎特利因使由卡巴胆碱预收缩的豚鼠气管松弛（IC50为2.1×10⁻⁴M），且以非特异性方式拮抗；卡巴胆碱（IC50为2.1×10⁻⁴M）和组胺（IC50为1.4×10⁻⁴M）在豚鼠回肠中诱导收缩；去氧肾上腺素（IC50为3.8×10⁻⁴M）在大鼠主动脉中引起反应。坎特利因以非竞争性、可逆（斜率为4.84）且浓度依赖性的方式拮抗回肠中组胺的累积浓度反应曲线（pD'2为3.82）。组胺和氯化钾诱导的强直性收缩也以浓度依赖性和可逆的方式受到抑制（IC50分别为7.2×10⁻⁵M和1.8×10⁻⁴M），这表明坎特利因可能作用于电压依赖性Ca²⁺通道。这一假设通过以下观察得到证实：坎特利因以浓度依赖性方式抑制（pD'2为3.35）去极化介质中氯化钙诱导的收缩。这些结果表明，坎特利因在平滑肌中产生非特异性解痉作用，在豚鼠回肠中，这种作用部分归因于抑制通过电压依赖性Ca²⁺通道的Ca⁺²内流。