Perez-Lloret Santiago, Merello Marcelo
Raul Carrea Institute for Neurological Research, Movement Disorders Section , Montañeses 2325 (1425), Buenos Aires , Argentina +54 11 57773200 ; +54 11 57773200 ;
Expert Opin Pharmacother. 2014 Jun;15(8):1097-107. doi: 10.1517/14656566.2014.903924. Epub 2014 Mar 27.
Adenosine A2A receptors are localized in the brain, mainly within the caudate and putamen nuclei of the basal ganglia. Their activation leads to stimulation of the 'indirect' pathway. Conversely, administration of A2A receptor antagonists leads to inhibition of this pathway, which was translated into reduced hypomotility in several animal models of parkinsonism.
In this review, the effects of two A2A receptor antagonists, istradefylline and tozadenant, on parkinsonian symptoms in animal and humans will be discussed.
Animal studies have shown potent antiparkinsonian effects for several A2A receptor antagonists, including istradefylline. In clinical trials, istradefylline reduced OFF time when administered with levodopa, but results are inconclusive. Results with tozadenant are scarce. Modification of thalamic blood flow compatible with reduced inhibition was noted in one small trial, followed by a significant reduction in OFF time in a larger one. Therefore, both drugs show promising efficacy for the reduction of OFF time in levodopa-treated Parkinson's disease patients, but further research is needed in order to obtain definitive conclusions.
腺苷A2A受体定位于大脑中，主要在基底神经节的尾状核和壳核内。其激活会导致“间接”通路受到刺激。相反，给予A2A受体拮抗剂会导致该通路受到抑制，这在几种帕金森病动物模型中转化为运动减少的减轻。
在本综述中，将讨论两种A2A受体拮抗剂，异他林和托扎替宁，对动物和人类帕金森病症状的影响。
动物研究表明，包括异他林在内的几种A2A受体拮抗剂具有强大的抗帕金森病作用。在临床试验中，异他林与左旋多巴合用时可减少“关”期时间，但结果尚无定论。托扎替宁的研究结果较少。在一项小型试验中观察到与抑制减轻相一致的丘脑血流改变，随后在一项大型试验中“关”期时间显著缩短。因此，这两种药物在减少左旋多巴治疗的帕金森病患者的“关”期时间方面均显示出有前景的疗效，但需要进一步研究以得出明确结论。
