Behavioral and biochemical characterization as antiparkinsonian drug of the new adenosine A2A antagonist 8-ethoxy-9-ethyladenine (Contributo in atti di convegno)

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  • Behavioral and biochemical characterization as antiparkinsonian drug of the new adenosine A2A antagonist 8-ethoxy-9-ethyladenine (Contributo in atti di convegno) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Pinna, Annalisa; Pontis, Silvia; Simola, Nicola; Volpini, Rosaria; Schintu, Nicoletta; Cristalli, Gloria; Morelli, Micaela (2010)
    Behavioral and biochemical characterization as antiparkinsonian drug of the new adenosine A2A antagonist 8-ethoxy-9-ethyladenine
    in Purines 2010 Meeting, Tarragona, Spagna, 30 maggio-2 Giugno
    (literal)
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  • Pinna, Annalisa; Pontis, Silvia; Simola, Nicola; Volpini, Rosaria; Schintu, Nicoletta; Cristalli, Gloria; Morelli, Micaela (literal)
Pagina inizio
  • 110 (literal)
Pagina fine
  • 111 (literal)
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  • Abstracts from Purines 2010 Meeting (literal)
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  • 6 (literal)
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  • 6 (literal)
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  • 2 (literal)
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  • ISI Web of Science (WoS) (literal)
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  • CNR, Institute of Neuroscience; University of Cagliari; University of Camerino (literal)
Titolo
  • Behavioral and biochemical characterization as antiparkinsonian drug of the new adenosine A2A antagonist 8-ethoxy-9-ethyladenine (literal)
Abstract
  • Background. Adenosine A2A receptor antagonists have emerged as an attractive nondopaminergic target in clinical trials aimed at evaluating improvement in motor deficits in Parkinson's disease (PD). Moreover, preclinical studies suggest that A2A receptor antagonists may slow the course of the underlying neurodegeneration of dopaminergic neurons. Previous studies assessing the 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 subtype and high antiparkinsonian activity in two in vivo rodent model of PD. 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 6-hydroxydopamine (6-OHDA) lesion and by verifying its neuroprotective role in MPTP mouse model. Results. In 6-OHDA-lesioned rats, acute administration of ANR 94, similarly to L-DOPA, counteracted impairments in the initiation of stepping movements, in the adjusting step and in the vibrissae-evoked forelimb placing induced by the lesion. Additionally, 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 SNc and in striatum, and 3) totally antagonized microglial activation (CD11b-positive cells) in SNc and partially in striatum. Conclusion. 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 antagonist. (literal)
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