title: Adenosine receptors and dyskinesia in pathophysiology.
abstract: First, the recent progress in the pathogenesis of levodopa-induced dyskinesia was described. Serotonin neurons play an important role in conversion from levodopa to dopamine and in the release of converted dopamine into the striatum in the Parkinsonian state. Since serotonin neurons lack buffering effects on synaptic dopamine concentration, the synaptic dopamine markedly fluctuates depending on the fluctuating levodopa concentration in the serum after taking levodopa. The resultant pulsatile stimulation makes the striatal direct-pathway neurons get potential that releases excessive GABA into the output nuclei of the basal ganglia. When levodopa is administered, the stored GABA is released, the output nuclei become hypoactive, and then dyskinesias emerge. Second, effects of adenosine A2A receptor antagonists on dyskinesia were described. It has been demonstrated that the expression of adenosine A2A receptors is increased in Parkinson's disease (PD) patients with dyskinesias, suggesting that blockade of A2A receptors is beneficial for dyskinesias. Preclinical studies have shown that A2A receptor antagonists reduce liability of dyskinesias in PD models. Clinical trials have demonstrated that A2A antagonists increase functional ON-time (ON without troublesome dyskinesia) in PD patients suffering from wearing-off phenomenon, although they may increase dyskinesia in patients with advanced PD.
authors.affiliation: Department of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan. Electronic address: masahiko_tomiyama@med.pref.aomori.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tomiyama
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy; D058915:Purinergic P1 Receptor Antagonists / Q000627:therapeutic use; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D007980:Levodopa
keywords: Clinical trial; Direct pathway; Dopamine D1 receptor; GABA; Serotonin; Troublesome dyskinesia; Wearing-off