Referenced in: none

Automatically associated channels: Cav2.2

Title: ZC88, a novel N-type calcium channel blocker from 4-amino-piperidine derivatives state-dependent inhibits Cav2.2 calcium channels.

Authors: Shuzhuo Zhang, Lujia Yang, Kang Zhang, Xiaoyan Liu, Weiwei Dai, Cheng Zhang, Zheng Yong, Jin Li, Jianquan Zheng

Journal, date & volume: Brain Res., 2015 Apr 24 , 1605, 12-21

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25681549

Abstract
Small molecular inhibitors of Cav2.2 have been reported for the treatment of neuropathic pain; however, low selectivity and side effects limit their further development. In our study, a series of new compounds were designed and synthesized by optimizing the 4-amino-piperidine template. The results show that ZC88 inhibits transiently expressed Cav2.2 in state-dependent manner in oocytes with an IC50 of 0.45 ± 0.09 μM. The steady-state inactivation relationship curve is shifted to more negative potentials for the calcium channels, suggesting that ZC88 blocks inactivated state of the channel. ZC88 does not present any remarkable effects on voltage-gated P/Q-type calcium channel currents, l-type calcium channel currents, potassium channel and sodium channel currents. Taken together, these in vitro data suggest that ZC88 is a voltage-dependent, subtype-selective Cav2.2 channel inhibitor and can achieve an improved therapeutic window over the relatively state-independent Cav2.2-selective inhibitor, which may have potential to be developed into a novel analgesic agent.