ANR 94 is an adenosine A2A receptor antagonist, which may have a potential therapeutic role in treating Parkinson’s disease.
8-ethoxy-9-ethyladenine (anr 94) had been characterized in vitro as an adenosine receptor antagonist. its chemical structure had been shown [1]. anr 94 has shown high selectivity and affinity for the human adenosine a2a receptor subtype and high antiparkinsonian activity in unilaterally 6-hydroxydopamine (6-ohda)-lesioned rats [2]. the ki value of anr 94 to the adenosine a2a receptor is 46 nm [1].adenosine is deeply involved in the control of motor behaviour and substantial evidences [1].in chinese hamster ovary (cho) cells stably transfected with human recombinant adenosine receptors, anr 94 was more selective than anr 82 at the adenosine a2a receptor, with a ki value of 46 nm [1]. treatment with anr 94 (0.5 mg/kg i.p. for 7 days) significantly prevented 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (mptp)-induced degeneration of th-positive cells (p < 0.0005) [2].in rats, at a dose of 5 mg/kg i.p., anr 94 did not modify spontaneous motility, whereas at higher doses (10 or 15 mg/kg), it induced hypermotility. anr 94 at a dose of 1 mg/kg had a low efficacy on catalepsy, whereas 5 mg/kg was fully effective. in deeply cataleptic rats, anr 94 at a dose of 5 mg/kg i.p. during the 90-min testing period significantly reversed the catalepsy induced by 0.2 mg/kg of haloperidol. from 30-60 min, the effect of anr 94 was maximal. the anticataleptic effect of anr 94 had a long duration of over 150 min. in 6-ohda-lesioned rats, anr 94 significantly increased the number of contralateral rotations induced by l-dopa (3 mg/kg); this effect lasted up to 120-130 min [2].
[1]. annalisa pinna, rosaria volpini, gloria cristalli, et al. new adenosine a2a receptor antagonists: actions on parkinson’s disease models. european journal of pharmacology, 2005, 512:157-164.
[2]. annalisa pinna, elisabetta tronci, nicoletta schintu, et al. a new ethyladenine antagonist of adenosine a2a receptors: behavioral and biochemical characterization as an antiparkinsonian drug. neuropharmacology, 2010, 58: 613-623.
