Effects of the adenosine A2A antagonist KW 6002 (istradefylline) on pimozide-induced oral tremor and striatal c-Fos expression: comparisons with the muscarinic antagonist tropicamide

Betz, Adrienne J.; Vontell, Regina; Valenta, John P.; Worden, Lila; Sink, Kelly S.; Font, Laura; Correa, Mercè; Sager, Thomas N.; Salamone, John D.

doi:10.1016/j.neuroscience.2009.05.040

Cited by 46 publications

(29 citation statements)

References 99 publications

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“…6-hydroxydopamine, MPTP) [27,58,59]. A 2A -receptor antagonists are effective in relieving parkinsonian muscular rigidity and tremor, as evidenced by suppression of haloperidol-induced rigidity [60] and inhibition of haloperidol- and pimozide-induced tremulous jaw movements [55,56,61]. In one study, motor effects of A 2A -receptor antagonism were accompanied by an inhibition of pimozide-induced increased expression of c-Fos in the VL neostriatum, the striatal area most closely associated with tremulous jaw movements [61].…”

Section: Motor Circuitry Of the Basal Gangliamentioning

confidence: 99%

“…A 2A -receptor antagonists are effective in relieving parkinsonian muscular rigidity and tremor, as evidenced by suppression of haloperidol-induced rigidity [60] and inhibition of haloperidol- and pimozide-induced tremulous jaw movements [55,56,61]. In one study, motor effects of A 2A -receptor antagonism were accompanied by an inhibition of pimozide-induced increased expression of c-Fos in the VL neostriatum, the striatal area most closely associated with tremulous jaw movements [61]. Other studies indicated that A 2A -receptor antagonists inhibited haloperidol-induced oxidative damage [47] and reversed haloperidol-related impairment of decision-making in the T-maze choice procedure (a possible model of antipsychotic-induced anhedonia) [62].…”

Section: Motor Circuitry Of the Basal Gangliamentioning

confidence: 99%

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Adenosine A<sub>2A</sub>-Receptor Antagonism and Pathophysiology of Parkinson’s Disease and Drug-Induced Movement Disorders

Kulisevsky

Poyurovsky

2011

Eur Neurol

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Parkinson’s disease and drug-induced movement disorders (DIMDs) have commonalities in etiology based on impaired dopamine-based neurotransmission. Adenosine A_2A-receptor antagonism may provide a new mechanism through which these disorders can be managed. In the motor circuit, tonic output from the globus pallidus and substantia nigra regulates movement via opposing excitatory and inhibitory inputs to the cerebral cortex through the direct and indirect pathways. Increased activity of the direct pathway increases movement via an inhibitory effect on thalamocortical projection neurons; increased activity of the indirect pathway has the opposite effect. Regulation of these pathways is mediated primarily by reciprocal inhibitory interactions between dopamine and adenosine receptors on neurons of these pathways. Adenosine A_2A receptors are colocalized with dopamine D₂ receptors on the indirect pathway neurons, with A_2A activation opposing the effect of D₂ activation. The A_2A receptors’ role in the pathophysiology of Parkinson’s disease and DIMDs is evidenced by the upregulation of A_2A receptors in patients with Parkinson’s disease and patients receiving long-term administration of dopamine blockers. Further, A_2A-receptor antagonists are effective in reversing parkinsonian motor deficits and extrapyramidal symptoms in animal models of Parkinson’s disease and DIMDs. Understanding the role of A_2A-receptor antagonism in the pathophysiology of Parkinson’s disease and DIMD has therapeutic implications.

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Section: Motor Circuitry Of the Basal Gangliamentioning

confidence: 99%

Section: Motor Circuitry Of the Basal Gangliamentioning

confidence: 99%

Adenosine A<sub>2A</sub>-Receptor Antagonism and Pathophysiology of Parkinson’s Disease and Drug-Induced Movement Disorders

Kulisevsky

Poyurovsky

2011

Eur Neurol

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“…8). Acute administration of several A 2A receptor antagonists significantly reversed jaw tremor induced by tacrine, pilocarpine, haloperidol, reserpine, and pimozide in rats, suggesting a beneficial use of these compounds as specific drugs against this parkinsonian symptom (Table 7.1; Betz et al 2009;Collins et al 2010Collins et al , 2012Collins-Praino et al 2011;Correa et al 2004;Pinna et al 2010;Salamone et al 2008;Simola et al 2004Simola et al , 2006Tronci et al 2007). Consistent with these findings, A 2A receptor antagonism or genetic deletion of the adenosine A 2A receptor significantly attenuated the TJMs induced by pilocarpine in mice (Table 7. 1;Salamone et al 2013).…”

Section: Effect Of a 2a Receptor Antagonist On Tremor Model Of Pdmentioning

confidence: 96%

Adenosine A2A Receptor Antagonists as Drugs for Symptomatic Control of Parkinson’s Disease in Preclinical Studies

Pinna

2015

Current Topics in Neurotoxicity

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Parkinson's disease (PD) is primarily a neurological basal ganglia (BG)-related disorder caused by progressive degeneration of the nigrostriatal dopaminergic neurons, which results in the cardinal motor symptoms of PD, including bradykinesia (slow movement and difficulty in initiation movement), resting tremor, muscle tone rigidity, postural instability, and sensorimotor integration deficits. The gold standard of PD therapy is characterized by the dopamine precursor L-DOPA however, after several years, this therapy leads to neuropsychiatric and motor complications, including fluctuations in motor response and dyskinesias, which develop in the majority of patients. Consequently, one of the main targets of research in PD is to identify alternative therapeutic approaches to ameliorate PD symptoms without inducing motor complications. Among the non-dopaminergic strategies for PD, one of the most promising is represented by adenosine A 2A receptor antagonists, due to the colocalization of these receptors and dopamine D 2 receptors in the striatopallidal neurons of the BG, which provides the anatomical basis for the existence of a functional antagonistic interaction between these receptors. Thus, extensive preclinical studies have been performed to prove the effectiveness of adenosine A 2A receptor blockade in counteracting the cardinal motor symptoms of PD.This chapter describes the effects of A 2A antagonists alone or in combination with L-DOPA against the cardinal motor symptoms of PD, using rodent and primate models of PD, and the main mechanisms responsible for these anti-parkinsonian effects. In addition, findings suggesting the potential utilization of A 2A antagonists, as adjunctive treatments to L-DOPA to reduce the L-DOPA induced wearing-off without modifying dyskinetic movements, have been reviewed. Keywords Parkinson's disease · Rodent models · Non-human primate models · Catalepsy · Rigidity · Tremor · 6-Hydroxydopamine lesion · MPTP lesion · A 2A receptor antagonists · Adenosine

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“…However, the loss of SCH58261 effects in GPR37-/-mice would alternatively be explained by the fact that GPR37-/-mice showed a reduced number of TJMs compared to WT animals. In order to discard this possibility and to demonstrate that it was still possible to regulate pilocarpine-induced TJMs in GPR37-/-mice, we evaluated the effects of the muscarinic receptor antagonist tropicamide, which has been previously described to be an effective blocker of this motor alteration caused by different drugs [18,19]. Accordingly, tropicamide was able to reduce a 72% (P < 0.01) the number of pilocarpine-induced TJMs in WT mice (Fig.…”

Section: Page 6 Of 16mentioning

confidence: 99%

Adenosine A2A receptor-mediated control of pilocarpine-induced tremulous jaw movements is Parkinson's disease-associated GPR37 receptor-dependent

Gandía

Morató

Štagljar

et al. 2015

Behavioural Brain Research

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Effects of the adenosine A2A antagonist KW 6002 (istradefylline) on pimozide-induced oral tremor and striatal c-Fos expression: comparisons with the muscarinic antagonist tropicamide

Cited by 46 publications

References 99 publications

Adenosine A<sub>2A</sub>-Receptor Antagonism and Pathophysiology of Parkinson’s Disease and Drug-Induced Movement Disorders

Adenosine A<sub>2A</sub>-Receptor Antagonism and Pathophysiology of Parkinson’s Disease and Drug-Induced Movement Disorders

Adenosine A2A Receptor Antagonists as Drugs for Symptomatic Control of Parkinson’s Disease in Preclinical Studies

Adenosine A2A receptor-mediated control of pilocarpine-induced tremulous jaw movements is Parkinson's disease-associated GPR37 receptor-dependent

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