Studies of the effects of carboxamide derivatives on the neural transmission

• Main Authors: Kuan-Chang Huang, 黃冠章
• Other Authors: Min-Jon Lin
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/5tfmsa

碩士 === 中山醫學大學 === 生物醫學科學學系碩士班 === 102 === Recent studies have shown that KCNQ openers have potential for the treatment of several central nervous system disorders, eg., epilepsy, migraine. The purpose of this study was to find new compounds of KCNQ opener. We used the structure of KCNQ (potassium channel, voltage-gated, KQT-like Subfamily) openers ML213 and retigabine as the template to search the possible KCNQ openers. Dr. Min-Jon Lin used the website Hit2lead.com to compare the structure of KCNQ openers and found that 21 derivatives of KCNQ opener. In these experiments the nerve-evoked muscle tension is inhibited by the treatment 2-amantyl-N~1~mesitylglycinamide hydrochloride (#0342；50μM). Treatment with #0342, 1 -cyclohexyl -N- mesitylprolinamide hydrochloride (#0335), 2 - (1-azepanyl) -N- mesitylbutanamide (#0331) and mesityl -2-peridinecarbox amide hydrochloride (#0321) produced the significant effect of titanic failure (50 Hz stimulation). In terminal spike recordings, the treatment of #0342, #0321 and #0335 produced the significant inhibition effect of sodium spikes. Therefore, the effects of the #0342, #0335 and #0321 are not similar to the KCNQ openers. These data suggested that #0342, #0335 and #0321 are more likely to be the sodium channel blockers than KCNQ modulators. Our initial research planning is to screen of new KCNQ openers from the predicted compounds. However these unexpected results indicate that the effects of #0342, #0321, and #0335 on the blocked of nerve – muscle conduction are more likely through the inhibition of sodium channels.