Pathophysiology of Motor Dysfunction in Parkinson’s Disease as the Rationale for Drug Treatment and Rehabilitation

Table 2

Nondopaminergic neurotransmitters involved in the pathogenesis of Parkinson’s disease and pharmacological agents potentially active or tested to counteract their deficit.

Neurotransmitter	Site	Symptom/sign	Drug
Acetylcholine	PPN, nucleus basalis of Meynert, striatum	Posture and gait disturbances, FOG, cognitive problems	Cholinesterase inhibitors, nicotinic receptor agonists
Adenosine	Striatum	Motor fluctuations, dyskinesia	Adenosine receptor antagonists, caffeine
GABA	GPe, STN	Motor fluctuations, dyskinesia	GAD gene therapy
Glutamate	Striatum, STN	Dyskinesia, FOG	NMDA receptor antagonists, AMPA receptor antagonists, mGluNAMs
Histamine	Striatum	Dyskinesia	H2 receptor antagonists
Noradrenaline	GPe, locus coeruleus	Balance and gait disturbances, FOG, dyskinesia	Methylphenidate, α2 receptor antagonists
Serotonin	Dorsal raphe nucleus, striatum, GP, SN	Motor fluctuations, dyskinesia	receptor antagonists

5-HT: serotonin receptor 1A; : adenosine receptor A2; AMPA: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; FOG: freezing of gait; GABA: gamma-aminobutyric acid; GAD: glutamic acid decarboxylase; GP: globus pallidus; GPe: external segment of the globus pallidus; mGluNAMs: metabotropic glutamate receptor negative allosteric modulators; NMDA: N-methyl-D-aspartate; PPN: pedunculopontine nucleus; SN: substantia nigra; STN: subthalamic nucleus.