Disease relevance of ZM241385

• Adenosine concentration-response experiments showed vasodilatation to be more pronounced during hypoxia (n = 9) than during normoxia (n = 9, P < 0.001) and the A(2A) receptor antagonist ZM241385 (20 nM, n = 5), attenuated hypoxia-induced vasodilatation while the selective A(2B) receptor antagonist MRS1754 (20 nM, n = 4), had no effect [1].
• 3. The selective A2A adenosine receptor antagonist ZM241385 (3 mg kg(-1), I.V.) had no effect upon the hindlimb vascular conductance or muscle contraction responses in the presence of the flow-limiting stenosis [2].
• However, microinjections of ZM241385 reduced the bradycardia evoked by stimulation of the ipsilateral aortic nerve [3].
• 5. Similarly, caffeine (50 mg kg(-1) day(-1), po), a nonselective adenosine receptor antagonist, and ZM241385 (25 mg kg(-1) bid), a more selective antagonist of the adenosine A(2A) receptor, diminished hepatic fibrosis in wild-type mice exposed to either CCl(4) or thioacetamide [4].

High impact information on ZM241385

• Two-way MLR-stimulated T cell proliferation was reduced by ATL313, a selective A(2A)R agonist in a dose-responsive manner ( approximately 70%; 10 nM), an effect reversed by the A(2A)R antagonist ZM241385 (100 nM) [5].
• Selective agonist (CGS21680) and antagonist (ZM241385) of A2A adenosine receptor were used in functional assays and cDNA probes for different sybtypes of adenosine receptors were used in Northern blot studies [6].
• Pretreatment with ZM241385 (A(2A)-Ado receptor antagonist) alone or in combination with MRS1706 (A(2B)-Ado receptor antagonist) resulted in a pure constriction upon Ado, whereas 8-cyclopentyltheophylline (CPT) (A(1)-Ado receptor antagonist) inhibited the constrictor response [7].
• The actions of caffeine (3.0, 10.0 and 30.0 mg/kg, i.p.), the A1 receptor antagonist DPCPX (1.0 and 3.0 mg/kg, i.p.) and the A2A receptor antagonist ZM241385 (0.5 and 1.0 mg/kg, i.p.) in relation to age-related effects on olfactory functions were also studied [8].
• Inhibition of CD49d expression was equally inhibited by ATL146e, added before or after TNF priming, and was reversed by incubation with the A(2A)AR-selective antagonist 4-[2-[7-amino-2-(2-furyl) (1, 2, 4)triazolo(2,3-a) (1, 3, 5)triazin-5-yl-amino]ethyl]-phenol (ZM241385; 100 nM) [9].

Biological context of ZM241385

• Unilateral microinjections of unlabelled ZM241385 into the nucleus tractus solitarius had no effect on baseline levels of arterial pressure, heart rate and phrenic nerve activity recorded in anaesthetized, artificially ventilated rats [3].
• Inhibition of glycolysis also increased (about three-fold) the extracellular accumulation of GABA, which was virtually unchanged by ZM241385 [10].
• For example, the antagonist ZM241385 demonstrates 0.23+/-0.03 nM affinity for the A(2A) receptor and has a functional potency of 0.26+/-0.04 nM determined using cAMP and 0.15+/-0.06 nM using CREB phosphorylation [11].

Anatomical context of ZM241385

• In contrast, ZM241385 had no effect on the depressor response or the reduction in phrenic nerve activity evoked by aortic nerve stimulation [3].
• We hypothesized that spinal cord functional and cytoarchitectural preservation from ATL-146e would be lost with simultaneous administration of the specific adenosine A(2A) antagonist ZM241385 (ZM), thus proving that adenosine A(2A) receptor activation is responsible for the protective effects of this compound [12].
• Each experiment tested a specific dose of an A1 receptor antagonist (8-cyclopentyltheophylline given via microinjection into the basal forebrain), an A2a receptor antagonist (ZM241385 via intraperitoneal administration), or both [13].
• Although ZM241385, a selective A(2A)R antagonist, significantly enhanced the increase in neutrophil elastase release and intracellular Ca(2+) concentrations in neutrophils stimulated with fMLP, this agent did not affect the endotoxin-induced TNF-alpha production by monocytes [14].
• A total of 10 microM AMP579 reduced neutrophil adherence to thrombin-stimulated endothelium (neutrophils/mm(2)) from 269+/-16 to 44+/-4 (P<0.05); this was reversed by ZM241385, but not by DPCPX or MRS1220 [15].

Associations of ZM241385 with other chemical compounds

• The nonselective AdoR antagonist xanthine amine congener (XAC), the A(2A)-selective antagonist ZM241385, the A(2B)-selective antagonists 3-N-propylxanthine (enprofylline) and 3-isobutyl-8-pyrrolidinoxanthine (IPDX), and the A(1)-selective antagonist cyclopentyl-1,3-dipropylxanthine (CPX) were used [16].
• The A2a receptor antagonist, ZM241385 had mixed effects on DAMGO-mediated inhibition, producing either a further inhibition or a reversal of the inhibition [17].
• Adenosine inhibited Fc epsilon RI-mediated tryptase release from HCMC in a dose-dependent manner, and this inhibitory effect was completely blocked by the A2a receptor antagonist ZM241385 [18].
• Coronary vasodilatation by CGS21680 was inhibited bythe A2A receptor antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo [2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385) [19].

Gene context of ZM241385

• Recent data have shown that selective adenosine A2A receptor antagonists (e.g., SCH 58261, ZM241385, and KW6002) or genetic inactivation of the receptor was effective in reversing signs of behavioral despair in the tail suspension and forced swim tests, two screening procedures predictive of antidepressant activity [20].
• By contrast, neither CPX nor ZM241385 had an effect on neovascularization [16].
• Exposition of insulin-deprived T lymphocytes to specific antagonist (ZM241385) of A2a receptor but not to specific antagonist (Alloxazine) of A2b receptor suppressed cAMP elevation and completely restored the proliferation potential of T cells [21].
• A2A adenosine receptor-selective antagonist, ZM241385 (10(-6) M), significantly attenuated the relaxation responses [22].
• Antagonism of coronary artery relaxation by adenosine A2A-receptor antagonist ZM241385 [22].

Analytical, diagnostic and therapeutic context of ZM241385

• In skin transplants, allograft survival was enhanced with ATL313, an effect blocked by ZM241385 [5].
• Microtubule-associated protein 2 expression was preserved in the sham and ATL-146E groups but was lost in the ATL + ZM, ZM241385, and control groups [12].
• The A2A selective antagonist, ZM241385, attenuated the coronary vasodilatation by CGS21680 and abolished the improved recovery of AO on reperfusion [23].

References