KF17837: A novel selective adenosine A2A receptor antagonist with anticataleptic activity

https://doi.org/10.1016/0014-2999(94)90551-7Get rights and content

Abstract

KF17837 is a novel selective adenosine A2A receptor antagonist. Oral administration of KF17837 (2.5, 10.0 and 30.0 mg/kg) significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine A2A receptor agonist, CGS 21680 (10 μg), in a dose-dependent manner. KF17837 also reduced the catalepsy induced by haloperidol (1 mg/kg i.p.) and by reserpine (5 mg/kg i.p.). These anticataleptic effects were exhibited dose dependently at doses from 0.625 and 2.5 mg/kg p.o., respectively. Moreover, KF17837 (0.625 mg/kg p.o.) potentiated the anticataleptic effects of a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 25 mg/kg i.p.) plus benserazide (6.25 mg/kg i.p.). These results suggested that KF17837 is a centrally active adenosine A2A receptor antagonist and that the dopaminergic function of the nigrostriatal pathway is potentiated by adenosine A2A receptor antagonists. Furthermore, KF17837 may be a useful drug in the treatment of parkinsonism.

References (37)

  • S.A. Josselyn et al.

    Behavioral effects of intrastriatal caffeine mediated by adenosinergic modulation of dopamine

    Pharmacol. Biochem. Behav.

    (1991)
  • C.D. Marsden et al.

    ‘On-off’ effects in patients with Parkinson's disease on chronic levodopa therapy

    Lancet

    (1976)
  • M.I. Martinez-Mir et al.

    Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease

    Neuroscience

    (1991)
  • S.N. Schiffmann et al.

    Distribution of adenosine A2 receptor mRNA in the human brain

    Neurosci. Lett.

    (1991)
  • S.J. Brown et al.

    Both A1 and A2a purine receptors regulate striatal acetylcholine release

    J. Neurochem.

    (1990)
  • S.J. Brown et al.

    Striatal A2 receptor regulates apomorphine-induced turning in rats with unilateral dopamine denervation

    Psychopharmacology

    (1991)
  • R.F. Bruns et al.

    Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes

    Mol. Pharmacol.

    (1986)
  • J.W. Daly et al.

    Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines

    Cell. Mol. Neurobiol.

    (1983)
  • Cited by (146)

    • Pyrazoloquinazolines: Synthetic strategies and bioactivities

      2015, European Journal of Medicinal Chemistry
      Citation Excerpt :

      Some of the important SARs are highlighted in the Fig. 7. In 2013, Catarzi et al., designed a number of 5-oxo-pyrazolo[1,5-i]quinazolines, bearing heteroaryl moiety at position-2 as hA3 AR [51] antagonists [52–54]. Study produced some interesting compounds endowed with good hA3 receptor affinity and high selectivity, being totally inactive at all the other AR subtypes.

    View all citing articles on Scopus
    View full text