CGS 21680 HCl

CGS 21680 HCl is a selective agonist of A2 adenosine receptor with IC50 value of 22nM [1].

In rat striatal membranes, CGS 21680 potently prevents ligands from binding to A2 adenosine receptors with IC50 value of 22nM. In the binding assay, CGS 21680 shows no effect to other putative neurotransmitter/neuromodulator sites in brain membranes such as adrenergic, dopamine and serotonin. In the rat heart model, CGS 21680 is effective in increasing coronary flow with EC25 value of 2nM [1].

In vivo, the hydrochloride salt of CGS 21680 has potent efficacy to decrease blood pressure in the anesthetized normotensive rat with ED50 value of 9μg/kg. It also causes heart rate increasing up to 15%. Besides that, CGS 21680 HCl significantly lower the blood pressure at dose of 10mg/kg in the spontaneously hypertensive rat. A transient elecation of heart rate is also observed at 30 min in the model [1].

References:
[1] Hutchison A J, Webb R L, Oei H H, et al. CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity. Journal of Pharmacology and Experimental Therapeutics, 1989, 251(1): 47-55.

Adenosine receptors and their ligands.[Pubmed:11111832]

Naunyn Schmiedebergs Arch Pharmacol. 2000 Nov;362(4-5):382-91.

The regulatory actions of adenosine are mediated via four subtypes of G protein-coupled receptors distinguished as A1, A2A, A2B and A3 receptors. Their presence on basically every cell makes them an interesting target for the pharmacological intervention in many pathophysiological situations. A large number of ligands have been synthesized over the last two decades and provide agonists and antagonists that are more or less selective for the known receptor subtypes. In addition, many radioligands are available in tritiated or radioiodinated form. The comparative pharmacological characterization of all four human adenosine receptor subtypes revealed that some of the compounds thought to be selective from data in other species have unexpected potencies at human receptors. As a result, compounds that exhibit high affinity to only one subtype are an exception. Although the selection of ligands is immense, it is less than satisfying for most subtypes of adenosine receptors.

Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output and vascular resistance in acute heart failure in the anaesthetized rat.[Pubmed:9605574]

Br J Pharmacol. 1998 Apr;123(8):1666-72.

1. The effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output, blood pressure, mean circulatory filling pressure (Pmcf), arterial and venous resistances, heart rate and left ventricular end-diastolic pressure were assessed in rats with acute heart failure by means of coronary artery occlusion. 2. Animals (n=6 in each group) were divided into five groups: group I, sham-operated vehicle-treated (0.9% saline; 0.018 mL min(-1)); groups II-V, subject to coronary artery occlusion and treated with vehicle (0.9% saline; 0.018 ml min(-1)) and CGS 21680 (0.1, 0.3 and 1.0 microg kg(-1) min(-1)), respectively. Haemodynamic measurements were taken one hour after completion of surgery, ninety minutes after coronary artery occlusion (except in group I), and fifteen minutes after infusion of saline or CGS 21680. 3. Baseline haemodynamic measurements before occlusion were found not to differ significantly between the different groups of animals. However, after occlusion, cardiac output, rate of rise in left ventricular pressure (+ dP/dt) and blood pressure were significantly reduced when compared to corresponding values in sham-operated animals. In addition, occlusion of the coronary artery resulted in a significant elevation in venous resistance, Pmcf and left ventricular end-diastolic pressure as compared to corresponding values in sham-operated animals. 4. Infusion with CGS 21680 at the highest dose significantly reduced blood pressure, arterial resistance and left ventricular end-diastolic pressure when compared to occluded vehicle-treated animals (group II). Administration of CGS 21680 at the highest dose also significantly increased cardiac output (28%) and heart rate (10%) in comparison to occluded vehicle-treated animals. In addition, the highest dose of CGS 21680 significantly reduced Pmcf (9%) and venous resistance (62%) in comparison to occluded vehicle-treated animals. Administration of CGS 21680 did not significantly affect +dP/dt when compared to occluded vehicle-treated animals. 5. The results from the present investigation indicate that occlusion of the coronary artery in rats results in a state of heart failure characterized by reduced arterial pressure and cardiac output, and increased venous resistance, Pmcf and left ventricular end-diastolic pressure. Administration of CGS 21680 to animals with acute heart failure resulted in increased cardiac output which was due to reduced venous resistance, as well as increased heart rate.

The selective adenosine A2 receptor agonist, CGS 21680, is a potent depressant of cerebral cortical neuronal activity.[Pubmed:2322828]

Brain Res. 1990 Feb 19;509(2):328-30.

The A2 selective adenosine receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) depressed the spontaneous, acetylcholine- and glutamate-evoked firing of rat cerebral sensorimotor cortical neurons. Iontophoretically applied CGS 21680 was equipotent with adenosine as a depressant and its actions were antagonized by 8-p-sulphophenyltheophylline applied from another barrel of the multibarrelled micropipette. The observation of a potent depressant action of a selective A2 receptor agonist suggests that A2 receptors are involved in the modulation of cerebral cortical neuronal firing by adenosine.