Steroidal Alkaloids with a Potent Analgesic Effect Based on N-type Calcium Channel Inhibition
Tian‐Zhen Xie, Lei Luo, Yun‐Li Zhao, Hao Li, Mei-Ling Xiang, Xu‐Jie Qin, Yingjie He, Yanyan Zhu, Zhi Dai, Zhao‐Jie Wang, Xin Wei, Yaping Liu, Li‐Xing Zhao, Ren Lai, Xiao‐Dong Luo
Abstract
Two distinctive alkaloids with 6/6/6/5/6/6 fused rings, in which a previously unidentified linkage of C-12/23 generates a rigid skeleton, resulting in a new subtype of steroidal alkaloid, were isolated from Veratrum grandiflorum. Compounds 1 and 2 showed potent analgesic effects in vivo, superior to the well-known analgesic, pethidine (Dolantin), likely by inhibiting CaV2.2 voltage-gated calcium channels.
Topics & Concepts
ChemistryPethidineAnalgesicAlkaloidCalcium channelPharmacologyIn vivoVoltage-dependent calcium channelCalciumIn vitroStereochemistryBiochemistryOrganic chemistryBiologyBiotechnologyMedicineDrug Transport and Resistance MechanismsHedgehog Signaling Pathway StudiesPharmacological Effects of Medicinal Plants