Calcium Channel Antagonists as Disease-Modifying Therapy for Parkinson's Disease: Therapeutic Rationale and Current Status.
Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated CaV1.3 subtype calcium channels in the pathogenesis of the disorder, and drugs with some selectivity for this ion channel (brain-penetrant dihydropyridine calcium channel blockers) are neuroprotective in animal models of the disease. Dihydropyridines have been safely used for decades to treat hypertension and other cardiovascular disorders. A phase II clinical trial found that isradipine was safely tolerated by patients with Parkinson's disease, and a phase III trial is currently underway to determine whether treatment with isradipine is neuroprotective and therefore able to slow the progression of Parkinson's disease. This manuscript reviews the current information about the use of dihydropyridines as therapy for Parkinson's disease and discusses the possible mechanism of action of these drugs, highlighting CaV1.3 calcium channels as a potential therapeutic target for neuroprotection in Parkinson's disease.
MIT Sloan Executive Education, Cambridge, MA, 02142, USA.
Tara
T
Swart
Neuroepidemiology and Ageing Research, School of Public Health, Imperial College London, Burlington Danes Building, Hammersmith Campus, DuCane Road, London, W12 0NN, UK. m.hurley@imperial.ac.uk.
Michael J
MJ
Hurley
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D015220:Calcium Channels / Q000378:metabolism*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D006801:Humans; D017275:Isradipine / Q000494:pharmacology / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018696:Neuroprotective Agents; D017275:Isradipine