Nakashima Y, Sugiyama S, Shindoh J, Taki F, Takagi K, Satake T, Ozawa T
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Arch Int Pharmacodyn Ther. 1990 Jul-Aug;306:130-8.
The effects of sodium channel blockers, a conventional one: tetrodotoxin, and clinically available ones: cibenzoline, flecainide and SUN 1165 [N-(2,6-dimethylphenyl)-8-pyrrolizidine-acetamide hydrochloride hemihydrate] on electrical field stimulation-induced and carbachol-induced guinea-pig tracheal smooth muscle contraction were investigated. Electrical field stimulation was performed at 50 V with 20 Hz and 0.8 msec square pulse duration. Carbachol (5 x 10(-8) M) was used for induction of tracheal contractions. All agents were administered before electrical field stimulation or carbachol administration. Electrical field stimulation-induced tracheal smooth muscle contraction was dose-dependently reduced by all sodium channel blockers used. The effects of sodium channel blockers on electrical field stimulation-induced contraction were greater than those on carbachol-induced contractions, except for SUN 1165 which reduced similarly both electrical field stimulation- and carbachol-induced contractions. These results indicate that the sodium influx is closely related to the acetylcholine release, resulting in smooth muscle contraction. Since the parasympathetic nervous system may be involved in the genesis of various pathological conditions, such as bronchial asthma, sodium channel blockers could contribute to the management of these conditions.
研究了钠通道阻滞剂（传统的一种：河豚毒素，以及临床上可用的：西苯唑啉、氟卡尼和SUN 1165 [N-(2,6-二甲基苯基)-8-吡咯烷乙酰胺盐酸盐半水合物]）对电场刺激诱导的和卡巴胆碱诱导的豚鼠气管平滑肌收缩的影响。电场刺激以50 V、20 Hz和0.8毫秒的方波持续时间进行。卡巴胆碱（5×10(-8) M）用于诱导气管收缩。所有药物均在电场刺激或卡巴胆碱给药前给予。所用的所有钠通道阻滞剂均能剂量依赖性地减轻电场刺激诱导的气管平滑肌收缩。除SUN 1165对电场刺激和卡巴胆碱诱导的收缩作用相似外，钠通道阻滞剂对电场刺激诱导的收缩作用大于对卡巴胆碱诱导的收缩作用。这些结果表明，钠内流与乙酰胆碱释放密切相关，从而导致平滑肌收缩。由于副交感神经系统可能参与各种病理状况（如支气管哮喘）的发生，钠通道阻滞剂可能有助于这些状况的治疗。
