Characterization of the antiparkinsonian effects of the new adenosine A2A receptor antagonist ST1535: Acute and subchronic studies in rats

Characterization of the Potent and Highly Selective A2AReceptor Antagonists Preladenant and SCH 412348 [7-[2-[4-2,4-Difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] in Rodent Models of Movement Disorders and Depression

“…Behavioral sensitization has been suggested to predict the development of dyskinesias after chronic treatment with L-Dopa (Tronci et al, 2007). Here, we found that L-Dopa produced behavioral sensitization after only 4 days of treatment in 6-OHDA-lesioned rats.…”

Unprecedented therapeutic potential with a combination of A2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson's disease

“…In rodent or primate models, when A 2A antagonists are given alone (i.e. as monotherapy) to severely DA-depleted animals they show only marginal activity [14][15][16], however, they are able to significantly potentiate dopaminergic treatment [17][18][19][20][21]. In the clinic, when the A 2A antagonist Istradefylline was given as monotherapy (i.e.…”

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

“…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).…”

“…Specifically, acute administration of several adenosine A 2A receptor antagonists induced no contralateral rotations per se, but significantly potentiated rotational behaviour induced by L-DOPA or apomorphine and by either dopamine D 1 or D 2 receptor agonists, in hemiparkinsonian rodents (Table 7. 1;Fenu et al 1997;Hodgson et al 2009;Koga et al 2000;Pinna et al 1996Pinna et al , 2005Pinna et al , 2010Pollack and Fink 1996;Rose et al 2007;Tronci et al 2007;Vellucci et al 1993;Weiss et al 2003). Furthermore, in hemiparkinsonian rats, more sophisticated measurements of akinesia, bradykinesia, and gait impairment have been assessed.…”

“…As described extensively in the Chap. 9 by Morelli, the influence of adenosine A 2A receptor blockade on dyskinesia has been investigated by means of validated experimental paradigms in which dyskinetic movements induced by chronic L-DOPA are expressed both in hemiparkinsonian rodents (sensitization of rotational behaviour and/or AIMs affecting parts of the body contralateral to the lesion) (Henry et al 1998;Lundblad et al 2003;Pinna et al 2001;Tronci et al 2007), and in parkinsonian MPTP-treated primates (dyskinetic movements affecting several parts of the body, similar to those observed in parkinsonian patients) (Bibbiani et al 2005). Summarizing the main findings concerning dyskinesia, it has been demonstrated that A 2A receptor antagonists, when administered alone, did not induce dyskinesia in both rodents and primates previously rendered dyskinetic by chronic L-DOPA (Grondin et al 1999;Hodgson et al 2010;Jones et al 2013;Kanda et al 1998;Lundblad et al 2002).…”