New adenosine A2A antagonist: Behavioral and Biochemical characterizations as antiparkinsonian drug

The search of alternative therapies for the treatment of Parkinson's disease (PD) is very active and adenosine A2A receptors, for their negative interaction with dopamine D2 receptors have became particularly attractive. Previous studies assessing the in vivo antiparkinsonian activity of a few 9-ethyladenine derivatives, demonstrated that the 8-ethoxy-9-ethyladenine (ANR 94) has high selectivity and affinity for the human adenosine A2A receptor subtype1 and high antiparkinsonian activity in two in vivo rodent model of PD2. In line with this evidence, we have confirmed the in vivo antiparkinsonian activity of the ANR 94 by assessing its role on limb akinesia, gait impairment and sensory-motor deficits produced by a 6-hydroxydopamine (6-OHDA) lesion3 and by verifying its neuroprotective role in the MPTP mouse model. In 6-OHDA-lesioned rats, acute administration of ANR 94, similarly to L-DOPA, counteracted the impairments in the initiation of stepping movements, in the adjusting step and in the vibrissae-evoked forelimb placing induced by the lesion. In addiction, administration of ANR 94 to subchronic MPTP-treated mice: 1) counteracted dopamine neuron degeneration in the substantia nigra pars-compacta (SNc), 2) partially prevented the astroglial response (GFAP positive cells) in the SNc and in the striatum, and 3) totally antagonized microglial activation (CD11b positive cells) in the SNc and partially in the striatum. These results, showed that the A2A receptor antagonist ANR 94 besides being beneficial in improving akinesia, gait deficits and sensory-motor impairments in PD also relieve astrogliosis and microgliosis, suggesting potential therapeutic application for this new synthesized A2A receptor antagonist.