KF17837 ((E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine), a potent and selective adenosine A2 receptor antagonist.

Abstract

8-(3,4-Dimethoxystryryl)-1,3-dipropyl-7-methylxanthine exhibited high affinity and selectivity for adenosine A2A receptors in binding assay using rat striatal A2A receptors labeled with [3H]2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosin e (CGS21680). The affinity was stereo selective: the E isomer, KF17837, showed a Ki value of 1.0 +/- 0.057 nM for the A2A receptors, whereas the Z isomer showed much lower affinity. KF17837 had 62-fold selectivity for the A2A receptors versus rat forebrain A1 receptors labeled with [3H]N6-cyclohexyladenosine (CHA). KF17837 was rapidly photoisomerized to form a stable equilibrium mixture (18% E - 82% Z), KF17837S, which showed Ki values of 7.9 +/- 0.055 nM and 390 +/- 68 nM for the A2A and A1 receptors, respectively. The inhibition type was competitive for [3H]CGS21680 binding. In rat pheochromocytoma PC12 cells KF17837S antagonized cAMP accumulation induced by 1 microM CGS21680 via the A2A receptors, with an IC50 value of 53 +/- 10 nM. cAMP accumulation induced by 10 microM 5'-N-ethylcarboxamidoadenosine via the A2B receptors in Jurkat cells (human T-cell line) was inhibited by KF17837S with an IC50 value of 1500 +/- 290 nM. These results indicate that KF17837S (and hence KF17837) is a highly potent and selective adenosine A2A receptor antagonist.

• Authors: H Nonaka, M Ichimura, M Takeda, Y Nonaka, J Shimada, F Suzuki, K Yamaguchi, H Kase
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 267 Issue 3 Pg. 335-41 (May 17 1994) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8088373 (Publication Type: Journal Article)

Chemical References

• Phenethylamines
• Purinergic P1 Receptor Antagonists
• Receptors, Cell Surface
• Xanthines
• 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
• KF 17837
• Cyclic AMP
• Adenosine

Topics

• Adenosine (analogs & derivatives, metabolism)
• Animals
• Binding, Competitive
• Corpus Striatum (metabolism)
• Cyclic AMP (metabolism)
• Male
• PC12 Cells
• Phenethylamines (metabolism)
• Purinergic P1 Receptor Antagonists
• Radioligand Assay
• Rats
• Rats, Wistar
• Receptors, Cell Surface (metabolism)
• Stereoisomerism
• Tumor Cells, Cultured
• Xanthines (metabolism, pharmacology)