Biomedical Engineering Reference
In-Depth Information
Therapeutic Potential of N-Type Voltage-Gated
Ca
2+
Channel
C. Gopi Mohan, Ashish Pandey, and Jignesh Mungalpara
Contents
1 Introduction .................................................................................. 290
2 Overview of Neuronal Voltage-Gated Ca
2+
Channels . .................................... 292
3 Structure and Mechanism of Action of N-Type
Voltage-Gated Ca
2+
Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
4 Review of Literature/Patent Survey on NCC Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
5 Chemoinformatics Study on NCC Blockers . . ............................................. 298
6 Need for NCC Blockers ..................................................................... 303
7 Conclusions and Future Prospective ........................................................ 304
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Abstract Voltage-gated N-type Ca
2+
channels (NCCs) play dominant roles in
neuropathic pain and cerebral ischemia. Ion channel therapeutics for many patho-
physiological conditions exists, which include: affective disorders, allergic
disorders, autoimmune diseases, epilepsy, hypertension, insomnia, pain, anesthesia,
anxiety, and stroke. Experimentally, it was well established that NCC inhibitory
activity is essential for the treatment of chronic neuropathic pain and stroke.
A major obstacle with these membrane proteins is that the atomic resolution
experimental structures are not available to understand the mode of small molecule
binding at its active sites. This article mainly focuses on Ca
2+
channel blockers
(CCBs), especially for NCCs, wherein lie some of the opportunities and advantages
associated with these channels as drug target.
Keywords N-type voltage-gated Ca
2+
channel Ziconotide Neuropathic pain
Stroke Descriptor QSAR
