title: Novel nondopaminergic targets for motor features of Parkinson's disease: review of recent trials.
abstract: Neurotransmitters other than dopamine are recognized as having modulatory roles within the basal ganglia and can influence the basal ganglia dopaminergic system to alter activity of the direct and indirect pathways. Many nondopaminergic neurotransmitter systems have been implicated in the mechanisms contributing to the motor features of Parkinson's disease (PD). Thus, it is now well established that neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic, opioidergic, histaminergic, and adenosinergic systems, are affected in the pathogenesis of PD. Nondopaminergic neurotransmitter systems are thus targets for the development of novel therapies for motor symptoms and motor complications in PD. Over the last 5 years, more than 20 randomized, control trials (RCTs) in PD investigating drugs that target several of these nondopaminergic neurotransmitter systems for the treatment of motor features have been completed. There are at least 15 additional RCTs that are ongoing or planned. Here, we review these RCTs to highlight the potential nondopaminergic pharmacological therapies for treatment of motor features of PD. Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development of these drugs will likely yield novel approaches with positive clinical implications.
authors.affiliation: Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Lorraine V
authors.initials: LV
authors.lastname: Kalia
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Brotchie
authors.forename: Susan H
authors.initials: SH
authors.lastname: Fox
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D058918:Adenosine A3 Receptor Antagonists / Q000627:therapeutic use; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002110:Caffeine / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D018757:GABA Modulators / Q000627:therapeutic use; D015316:Genetic Therapy; D005968:Glutamate Decarboxylase / Q000235:genetics; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D018722:Nicotinic Agonists / Q000627:therapeutic use; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D043705:Receptor, Adenosine A2A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D018759:Adrenergic Uptake Inhibitors; D000978:Antiparkinson Agents; D002800:Cholinesterase Inhibitors; D018757:GABA Modulators; D006635:Histamine H2 Antagonists; D018722:Nicotinic Agonists; D010726:Phosphodiesterase Inhibitors; D043705:Receptor, Adenosine A2A; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; D002110:Caffeine; D005968:Glutamate Decarboxylase; D000109:Acetylcholine