Disease relevance of Tocris-0671

• Moreover, the PGE2-related mechanisms for regulating sleep-wake activities may be different from those producing hyperthermia, because AH 6809 at 21 pmol/min had no primary effect on brain temperature and did not antagonize the hyperthermia produced by the PGE2 infusion [1].
• Both AH 6809 and Rp-cAMP were found to prevent the later development of radiographically documented heterotopic ossification in 15 out of 16 animals, thus identifying prostaglandins as being required for the development of ectopic bone [2].

Psychiatry related information on Tocris-0671

• These changes can be explained by AH 6809 antagonizing the endogenous PGE2 that acts to augment wakefulness in the brain [1].

High impact information on Tocris-0671

• AH 6809 in saline was infused continuously into the third ventricle of freely moving rats at a rate of 2.1, 6.3, and 21 pmol/min from 2300 to 0500 hr [1].
• Studies with the E prostanoid (EP) 2 receptor antagonist AH-6809 and EP2-null macrophages indicated that this was due in part to the previously unknown ability of treprostinil to stimulate the EP2 receptor [3].
• The effect of indomethacin on AM phagocytosis could be mimicked by an EP2 antagonist, AH-6809, and exogenous addition of PGE(2) reversed the beneficial effects of indomethacin in vitro [4].
• In contrast, the facilitation by 8-iso-PGE(1) and 8-iso-PGE(2) of G-CSF release was unaffected by AH 6809 and the selective EP(4)-receptor antagonist L-161,982 [4'-[3-butyl-5-oxo-1-(2-trifluoromethyl-phenyl)-1,5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2-sulfonic acid (3-methyl-thiophene-2-carbonyl)-amide] [5].
• AH 6809 (6-isopropoxy-9-oxoxanthine-2-carboxylic acid), an EP(1)-/EP(2)-/DP-receptor blocking drug, antagonized the inhibitory effect of 8-iso-PGE(1) and 8-iso-PGE(2) on GM-CSF output with an affinity consistent with an interaction at prostanoid receptors of the EP(2)-subtype [5].

Biological context of Tocris-0671

• The G(0)/G(1) accumulation caused by AH-6809 seems to be intracellular Ca(2+) concentration ([Ca(2+)](i)) dependent, because a 6-h 1 microM thapsigargin treatment allowed G(0)/G(1)-arrested cells to enter S phase [6].
• Furthermore, inhibition of PGE2 receptors with AH-6809 attenuated vasodilation to H2O2 similar to that produced by indomethacin [7].
• An EP2 receptor antagonist (AH 6809) did not suppress the PGE(2)-induced MUC5AC gene expression or MUC5AC mucin [8].

Anatomical context of Tocris-0671

• We studied the role of EP(1) and EP(4) PGE(2) subtype receptor antagonists AH-6809 and AH-23848B, respectively, in serum-induced 3T6 fibroblast proliferation [6].
• The effect of sulprostone was not affected by AH 6809, that antagonizes EP1- and EP2-receptors, suggesting the presence of presynaptic EP3-receptors on the cholinergic nerve endings [9].
• Pretreatment of human monocytes with 10 microM AH 6809 did not affect LPS-induced TNF alpha generation but produced a parallel 3.5 fold rightwards shift of the PGE2 concentration-response curve [10].
• Competition binding studies using AH 6809 (EP1 antagonist), butaprost (EP2 agonist), M/+B 28,767 (EP3 agonist), and AH 23848B (EP4 antagonist) suggested that the retinal vessels of the newborn contained approximately equal number of EP1 and EP2 receptor subtypes whereas the main receptor subtype in the adult vessels was EP1 [11].

Associations of Tocris-0671 with other chemical compounds

• Additionally, the EP2 antagonist AH-6809 abrogated the inhibitory effects of both PGE(2) and butaprost [12].
• Rabbits were preadministered the PGE2/PGD receptor antagonist AH 6809 or the cAMP antagonist Rp-cAMP prior to undergoing the regimen of limb immobilization and passive exercise [2].
• 3. The spasmogenic effects of 8-iso PGE(2) were markedly attenuated by the TP-receptor blocker ICI 192605 and by the EP-receptor blocker AH 6809 (-log K(B)=8.4 and 5.7, respectively) [13].
• These contractions were sensitive to the prostanoid TP receptor antagonist ICI 192,605 (0.1-1 microM), but not the EP prostanoid receptor antagonist AH-6809 (50 microM), or the leukotriene receptor antagonists monteleukast or ICI 198,615 (both 1 microM) [14].
• However, the xanthone derivative AH 6809 blocks the inhibitory action of PGD2 but does not affect EP 035, EP 157 and PGI2 and its structural analogues [15].

Gene context of Tocris-0671

• These effects were associated with a decrease in cyclin D and E levels in AH-6809-treated 3T6 cells and lower cyclin A levels in AH-23848B-treated fibroblasts with respect to control cells [6].
• The concentration-response curve of PGE2 was marginally shifted to the right by the EP1 receptor antagonist AH 6809 (6-isopropoxy-9-oxoxanthene-2- carboxylic acid; apparent pA2 3.97) and by the TP receptor antagonist vapiprost (4.50) [16].
• PGE2-mediated inhibition was not antagonized by the selective prostanoid EP1-receptor antagonists AH 6809 (10 microM) or SC-19220 (30 microM), nor did these agents alone affect basal or field-stimulated 3H-NE release [17].
• The EP1/EP2 receptor antagonist AH-6809 (20 microM) had no effect on SP release produced by PGE(2) (0.14 microM) from an isolated rat renal pelvic wall preparation [18].
• Neither pEC(50) nor maximum of PGE(2) and 17-phenyl-trinor-PGE(2) concentration-response curves were modified by the DP/EP(1)/EP(2) receptor antagonist AH 6809 (1 micro M) [19].

Analytical, diagnostic and therapeutic context of Tocris-0671

• In anesthetized rats, the afferent renal nerve activity (ARNA) responses to butaprost 700 +/- 100 and PGE(2).780 +/- 100%.s (area under the curve of ARNA vs. time) were unaffected by renal pelvic perfusion with AH-6809 [18].

References