Calcium ion channels: challenges and successes in drug discovery

There are both opportunities and challenges in developing improved or novel therapeutics based on targeting voltage-gated calcium channels. Calcium channels are technically difficult with respect to target-based drug discovery but unquestionably are key points for influencing human physiology and pathophysiology. Many marketed drugs, including nifedipine, nimodipine, ethosuximide, pregabalin, and ziconotide, exert therapeutic efficacy via inhibition of calcium channels. Although there is no obvious path to improving these existing drugs, recent clinical results with dihydropyridine drugs point to testable strategies for treatment of Parkinson's disease and possibly other CNS disorders by inhibiting L-type calcium channels. Roles of T-type calcium channels in pain and in abnormal sleep are plausible and may soon be tested with clinical trials of novel therapeutics. Success with any of these trials certainly will be followed by intensive efforts for further refinements around the target class. WIREs Membr Transp Signal 2013, 2:85–104. doi: 10.1002/wmts.71 For further resources related to this article, please visit the WIREs website.