著者

Kim Ki Jung Cho Hyeong Seok Choi Se Joon Jeun Seung Hyun Kim Seong Yun Sung Ki-Wug

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.107, no.1, pp.57-65, 2008

被引用文献数

5

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The pharmacological action of riluzole, a drug that has been approved as a neuroprotective agent for the treatment of amyotrophic lateral sclerosis, has not yet been established. We examined the effects of riluzole on 5-hydroxytryptamine (5-HT)₃ receptors in NCB-20 neuroblastoma cells using the whole-cell voltage clamp technique combined with a fast drug application method. Co-application of riluzole (1 – 300 μM, 5 s) produced a dose-dependent reduction in peak amplitudes and in the rise slope of the currents induced by 2 μM 5-HT. In addition, 5-HT₃–mediated currents evoked by dopamine, a partial 5-HT₃–receptor agonist, were inhibited by riluzole co-application. These inhibitory effects were clearly shown at low concentrations of 5-HT. The decay time constants of the receptor desensitization and deactivation were also significantly attenuated by riluzole. G-protein inhibitors (pertussis toxin and guanosine 5'-[β-thio] diphosphate) did not completely block these inhibitory actions of riluzole. These results indicate that riluzole inhibits 5-HT₃–induced ion currents directly by slowing channel activation in NCB-20 neuroblastoma cells.<br>