Towards the discovery of novel T-type calcium channel blockers.
Despite their presence in many tissues and their potential implication in various disease states, low-voltage activated T-type calcium channels (T-channels) have only recently become targets of interest. Unfortunately, the lack of selective T-channel blockers has hampered further characterisation of these channels. The recent availability of cloned T-channels, the Ca(V)3 proteins, facilitates identification of novel T-channel blockers. Also, studies performed in knockout animals have fostered novel interest. Selective inhibition of T-channels may have clinical importance in cardiovascular diseases, some forms of epilepsy, sleep disorders, pain and possibly cancer. This review focuses on novel research approaches to discover potent and selective T-channel modulators. These molecules may be potential drugs for treating human diseases, as well as important tools to decipher the physiological role of these channels.
Lory
Philippe
P
Institut de Génomique Fonctionnelle, Département de Physiologie, CNRS UMR 5203, INSERM U661, IFR3, Universités de Montpellier I and II, Montpellier cedex 05, France. philippe.lory@igf.cnrs.fr
Chemin
Jean
J
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D001095:Arachidonic Acids / Q000502:physiology; D001321:Autistic Disorder / Q000188:drug therapy / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D002412:Cations / Q000494:pharmacology; D015195:Drug Design; D063388:Endocannabinoids; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D053284:Polyunsaturated Alkamides; D012604:Scorpion Venoms / Q000494:pharmacology; D020919:Sleep Disorders, Intrinsic / Q000188:drug therapy / Q000378:metabolism
D000700:Analgesics; D000927:Anticonvulsants; D001095:Arachidonic Acids; C479952:CACNA1H protein, human; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002317:Cardiovascular Agents; D002412:Cations; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D012604:Scorpion Venoms; C118444:kurtoxin; D002118:Calcium; C078814:anandamide