Drugs in development for Parkinson's disease: an update.
The current development of emerging pharmacological treatments for Parkinson's disease (PD), front preclinical to launch, is summarized. Advances over the past year are highlighted, including the significant progress of several drugs through various stages of development. Several agents have been discontinued from development, either because of adverse effects or lack of clinical efficacy. The methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B inhibitor rasagiline have both been launched. With regard to the monoamine re-uptake inhibitors, many changes have been witnessed, with new agents reaching preclinical development and pre-existing ones being discontinued or having no development reported. Of the dopamine agonists, many continue to progress successfully through clinical trials. Others have struggled to demonstrate a significant advantage over currently available treatments and have been discontinued. The field of non-dopaminergic treatments remains dynamic. The alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists remain in clinical trials. Trials of the neuronal' synchronization modulator levetiracetam are at an advanced stage, and there has also been a new addition to the class (ie, seletracetam). There has been a change in the landscape of neuroprotective agents that modulate disease progression. Candidates from the classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors have been discontinued, or no development has been reported, and the mixed lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein oligomerization inhibitors, remain in development.
Johnston
Tom H
TH
Toronto Western Research Institute, Toronto Western Hospital, University Health Network, 399 Bathurst Street, MC 11-419, Toronto, ON M5T 2S8, Canada.
Brotchie
Jonathan M
JM
D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015195:Drug Design; D004345:Drug Industry; D006801:Humans; D015394:Molecular Structure; D020734:Parkinsonian Disorders / Q000188:drug therapy*
D000978:Antiparkinson Agents