Targeting N-type and T-type calcium channels for the treatment of pain.
Severe chronic pain afflicts a large number of people worldwide but satisfactory relief from such pain is difficult to achieve with drugs that are currently available, and so there is a great need for the development of new, efficacious and safe analgesics. Voltage-gated calcium-permeable ion channels are multi-subunit complexes that regulate neuronal excitability, action-potential firing patterns and neurotransmission in nociceptive pathways. Although multiple subtypes of voltage-gated calcium channels exist, pharmacological and ion-channel gene knockdown approaches in animals have revealed N-type and T-type calcium channels to be particularly attractive molecular targets for the discovery and development of new analgesic drugs. The recent approval of Prialt (Elan Pharmaceuticals) provides the ultimate target validation for N-type calcium channels, namely proof that they are key regulators of nociceptive signaling in humans.
McGivern
Joseph G
JG
Department of HTS-Molecular Pharmacology, Amgen, Thousand Oaks, CA 91320, USA. mcgivern@amgen.com
D000208:Acute Disease; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D002908:Chronic Disease; D006801:Humans; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology; D020960:omega-Conotoxins / Q000494:pharmacology / Q000627:therapeutic use
D000700:Analgesics; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D020960:omega-Conotoxins; C078452:ziconotide