title: Pharmacotherapies for Parkinson's disease symptoms related to cholinergic degeneration.
abstract: Dopamine depletion is one of the most important features of Parkinson's Disease (PD). However, insufficient response to dopaminergic replacement therapy suggests the involvement of other neurotransmitter systems in the pathophysiology of PD. Cholinergic degeneration contributes to gait impairments, cognitive impairment, psychosis, and REM-sleep disturbances, among other symptoms. Areas covered: In this review, we explore the idea that enhancing cholinergic tone by pharmacological or neurosurgical procedures could be a first-line therapeutic strategy for the treatment of symptoms derived from cholinergic degeneration in PD. Expert opinion: Rivastigmine, a drug that increases cholinergic tone by inhibiting the enzyme cholinesterase, is effective for dementia, whereas the use of Donepezil is still in the realm of investigation. Interesting results suggest the efficacy of these drugs in the treatment of gait dysfunction. Evidence on the clinical effects of these drugs for psychosis and REM-sleep disturbances is still weak. Stimulation of the pedunculo-pontine tegmental nuclei (which provide cholinergic innervation to the brain stem and subcortical nuclei) has also been used with some success for the treatment of gait dysfunction. Anticholinergic drugs should be used with caution in PD, as they may aggravate cholinergic symptoms. Notwithstanding, in some patients they might help control parkinsonian motor symptoms.
authors: a Institute of Cardiology Research , University of Buenos Aires, National Research Council (CONICET-ININCA) , Buenos Aires , Argentina.
authors: Santiago
authors: S
authors: Perez-Lloret
authors: b Parkinson's Disease and Movement Disorders Clinic, Neurology Department , CEMIC University Hospital , Buenos Aires , Argentina.
authors: María Cecilia
authors: MC
authors: Peralta
authors: c Laboratory of Molecular Neurobiology , Institute for Biomedical Research, UCA-CONICET, Faculty of Medical Sciences , Buenos Aires , Argentina.
authors: Francisco J
authors: FJ
authors: Barrantes
mesh_terms: D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D059329:Cholinergic Neurons / Q000187:drug effects / Q000473:pathology*; D002986:Clinical Trials as Topic / Q000379:methods; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D003704:Dementia / Q000175:diagnosis / Q000178:diet therapy / Q000453:epidemiology; D000077265:Donepezil; D005684:Gait / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology
chemical_list: D018678:Cholinergic Agents; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: Parkinson’s disease; acetylcholine; cholinergic dysfunction; neurodegeneration; pathophysiology; treatment