PBF509, an Adenosine A Receptor Antagonist With Efficacy in Rodent Models of Movement Disorders.

Adenosine A receptor (AR) antagonists have emerged as complementary non-dopaminergic drugs to alleviate Parkinson's disease (PD) symptomatology. Here, we characterize a novel non-xhantine non-furan AR antagonist, PBF509, as a potential pro-dopaminergic drug for PD management. First, PBF509 was shown to be a highly potent ligand at the human AR, since it antagonized AR agonist-mediated cAMP accumulation and impedance responses with K values of 72.

Antiparkinsonian Efficacy of Guanosine in Rodent Models of Movement Disorder.

Guanosine (GUO) is a guanine-based purine nucleoside with important trophic functions and promising neuroprotective properties. Although the neuroprotective effects of GUO have been corroborated in cellular models of Parkinson's disease (PD), its efficacy as an antiparkinsonian agent has not been fully explored in PD animal models. Accordingly, we evaluated the effectiveness of GUO in reversing motor impairments in several rodent movement disorder models, including catalepsy, tremor, and hemiparkinsonism.

Striatal adenosine A2A receptor expression is controlled by S-adenosyl-L-methionine-mediated methylation.

Adenosine A2A receptor (A2AR) is a G protein-coupled receptor enriched in the striatum for which an increased expression has been demonstrated in certain neurological diseases. Interestingly, previous in vitro studies demonstrated that A2AR expression levels are reduced after treatment with S-adenosyl-L-methionine (SAM), a methyl donor molecule involved in the methylation of important biological structures such as DNA, proteins, and lipids. However, the in vivo effects of SAM treatment on A2AR expression are still obscure.

Dopamine D(2) receptor-mediated modulation of adenosine A(2A) receptor agonist binding within the A(2A)R/D(2)R oligomer framework.

The molecular interaction between adenosine A2A and dopamine D2 receptors (A2ARs and D2Rs, respectively) within an oligomeric complex has been postulated to play a pivotal role in the adenosine-dopamine interplay in the central nervous system, in both normal and pathological conditions (e.g. Parkinson's disease).

Caffeine improves attention deficit in neonatal 6-OHDA lesioned rats, an animal model of attention deficit hyperactivity disorder (ADHD).

Nowadays the pharmacological treatment of the attention deficit hyperactivity disorder (ADHD) is based on amphetamine derivatives (i.e. methylphenidate).