Disease relevance of CGS21680

• Intraperitoneal coadministration of the non-competitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine (0.16 mg/kg) or the competitive NMDA antagonist CGP 37849 (4 mg/kg) completely reversed CGS 21680C-induced catalepsy, while lower doses of both NMDA antagonists induced no or only weak anticataleptic effects [1].
• Intra-arterial infusion of CGS 21680C, an A2-adenosine receptor agonist, also produced a fetal tachycardia of approximately 86 beats/min above the control mean and increased intrinsic fetal heart rate by approximately 38 beats/min [2].

High impact information on CGS21680

• During a steady-state infusion of CSC, the animals received 1000 micrograms/kg of the adenosine A2a receptor agonist CGS 21680C [the sodium salt of 2-p-(2-carboxyethyl) phenylethylamino-5'-N-ethylcarboxamidoadenosine] i.v. over 15 min [3].
• For each individual rat, the CGS 21680C-provoked reduction in blood pressure was related to the blood concentration of the agonist according to the sigmoidal Emax model [3].
• 4. Both the nicotinic acetylcholine receptor agonist, 1,1-dimethyl-4-phenylpiperazinium, and the A2a adenosine receptor agonist, CGS 21680C, increased evoked [3H]-ACh release, but only CGS 21680C potentiated the facilitatory effect of CGRP [4].
• In addition to a reduction in A2 receptor number, increased heart rates were seen on day 1 and 2 in both the CGS 21680C- and CGS 22989-treated animals and a mild stimulation of the renin angiotensin system occurred with CGS 21680C [5].
• On the other hand, the adenosine A2 selective agonist, CGS 21680C (0.37 nmol/kg/min i.r.a), elicited monophasic renal vasodilation and this effect on renal blood flow was unaffected by EDRF inhibitor [6].

Biological context of CGS21680

• Furthermore, blockade of the beta adrenergic receptor with metoprolol (1 mg/kg, i.v.) significantly attenuated the increase in heart rate produced by NECA, CGS 21680C and CGS 24012 [7].
• Both compounds were considerably less active at A1 receptors with CGS 21577 and CGS 21680C having respective IC50 values of 0.76 and 3.1 microM [8].
• Hindquarter, renal and mesenteric vascular resistances were significantly reduced by both CGS 21680C and CGS 24012, whereas only mesenteric vascular resistance was reduced with NECA [7].
• At equihypotensive doses, both CGS 21680C and CGS 24012 produced significant increases in cardiac output, but NECA had no effect [7].
• Effects of a putative A2-adenosine receptor agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamide-adeno sine (CGS 21680C) on force of contraction, protein phosphorylation, cyclic adenosine monophosphate (cAMP) content, and the activity of phosphodiesterase (PDE) isoenzymes in guinea pig ventricular (GPV) preparations were studied [9].

Anatomical context of CGS21680

• The adenosine A2a receptor localization to striatopallidal neurons suggests that a selective activation of the striatopallidal efferent pathway is involved in the expression of catalepsy induced by intrastriatal infusion of CGS 21680C [1].
• CGS 21680C (1-100 microM) did not affect force of contraction in isolated electrically driven papillary muscles and was ineffective in increasing phosphorylation of phospholamban (PLB) and the inhibitory subunit of troponin (TnI) in [32P]-labeled GPV cardiomyocytes [9].
• Stimulation of PMNs with CGS-21680C, but not with cyclohexyladenosine, inhibited both the adhesion of PMNs to the endothelium and the PMN-induced vasoconstriction [10].

Associations of CGS21680 with other chemical compounds

• The increase in cAMP content by CGS 21680C or rolipram is ineffective in increasing phosphorylation of PLB and TnI [9].
• The highly selective A2a agonist 2-[p-(2-carboxyethyl)phenyl amino]-5'-N-ethyl carboxamido adenosine (CGS-21680C, 10 microM) and A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 10 microM) had no vasodilatory effect [11].

Gene context of CGS21680

• The adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamideadeno sine (CGS 21680C, 3 nM), but not the adenosine A1 receptor agonist, R-N6-phenylisopropyl adenosine (R-PIA, 300 nM), partially blocked the DMPP (1 microM) facilitation [12].
• Marked elevation in plasma renin activity occurred with CGS 24012 and CGS 21680C, whereas no change was seen after NECA [7].

References