Adenosine A1 receptor is a member of the adenosine receptor group of G protein-coupled receptor. Specifically, the A1 receptor is relevant to sleep promotion by inhibiting cholinergic neurons in the basal forebrain that promote arousal. Besides, the A1 receptor also exists in the smooth muscle of the whole vascular system. Endogenous adenosine A1 and A2A receptors are thought to play a role in regulating myocardial oxygen consumption and coronary blood flow. Moreover, stimulating the A1 receptor reduces the conduction of electrical pulse and inhibiting the function of pacemaker cells. So, it can inhibit the heart rate and decrease the heart rate. This makes adenosine a useful drug for the treatment and diagnosis of tachyarrhythmia or tachyarrhythmia.

Furthermore, A1AR activation can cause mechanisms involving Gi, PKC, and extracellular signal-regulated kinase (ERK) activation. And this results in preventing renal IR injury in vivo and in vitro models. Here, we will introduce a potent and selective irreversible A1 adenosine receptor (A1AR) antagonist, FSCPX.

FSCPX is a Selective Irreversible Antagonist of A1AR.

First of all, FSCPX is a selective irreversible antagonist of A1AR, with low nanomolar potency for binding to the A1AR. Meanwhile, FSCPX modifies the effect of NBTI by reducing the interstitial adenosine level in the guinea pig atrium. NBTI is a nucleoside transport inhibitor.

In the second place, FSCPX irreversibly blocks the binding of [3H]DPCPX, with an IC50 of 11.8 nM in DDT1 MF2 cells. Nonetheless, FSCPX with 20 μM for 48 h prevents the increased resistance against necrosis and apoptosis in A1AR-overexpressing LLC-PK1 cells. Particularly, FSCPX reverses the upregulation of HSP27 mRNA and protein in A1AR-overexpressing LLC-PK1 cells. Interestingly, FSCPX has no effect on the mRNA or protein for HSP70.

All in all, FSCPX is a Selective Irreversible Antagonist of A1AR.


H T Lee, et al. Kidney Int. 2007 Jun;71(12):1249-61.