title: Recent progress in the discovery and development of N-type calcium channel modulators for the treatment of pain.
abstract: The importance of voltage-gated calcium channels (VGCCs) in basic physiological processes such as cardiac and neurological function has generated intense interest in these proteins as targets of pharmacological intervention. N-type calcium channels are a subset of VGCCs distinguished by their physiology, pharmacology and significance to the pathology of chronic pain. Despite decades of investigation, only a single drug targeting N-type channel function has entered the marketplace. This review will summarize our current understanding of the biology, physiology and pharmacology of N-type calcium channels and the implication of these features for therapeutic intervention. From this basis of understanding, recent efforts to discover and develop peptide based and small molecule modulators of N-type calcium channel function will be discussed.
authors.affiliation: Research & Translational Medicine, Zalicus Inc., Cambridge MA, USA.
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000502:physiology; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008969:Molecular Sequence Data; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use
chemical_list: D020864:Calcium Channels, N-Type; D007211:Indoles; D010455:Peptides; D010879:Piperazines; D010880:Piperidines
keywords: CACNA1B; Ca(V)2.2; Inactivation; N-type calcium channel; Pain; State-dependent; Use-dependent; Voltage-gated calcium channel; ω-Conotoxin