Disease relevance of AH23848

• Pretreatment with AH23848 30 min before coronary artery occlusion reduced the number of ischaemia-induced extrasystoles to 339 +/- 111 compared with 736 +/- 153 in the control group [1].
• Late intervention with AH23848, 25 min after the onset of myocardial ischaemia did not significantly alter the incidence of reperfusion-induced ventricular fibrillation; 70% of the control group died and 60% of those that received AH23848 [1].
• Administration of both an EP4 antagonist [AH23848, (4Z)-7-[(rel-1S,2S,5R)-5-((1,1'-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid] and EP4 knockdown with intrathecally delivered short hairpin RNA attenuates inflammation-induced thermal and mechanical behavioral hypersensitivity, without changing basal pain sensitivity [2].
• Effect of the specific thromboxane receptor blocking drug AH23848 in patients with angina pectoris [3].

High impact information on AH23848

• Finally, AH23848 significantly decreased the renin release by kidneys of the three strains.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• The formation of cAMP by PGE2 was concentration-dependently inhibited by the EP4 receptor-selective antagonist AH23848 [5].
• The antithrombotic effect of a specific thromboxane A2 receptor blocking drug, AH23848, on radio-labelled platelet deposition in mature Dacron aorto-bifemoral grafts has been evaluated in patients [6].
• AH23848 also reduces the PGE(2)-mediated sensitization of capsaicin-evoked currents in DRG neurons in vitro [2].
• Since AH23848 inhibited PGE2-induced cAMP formation in U-937 cells to a similar extent as in Jurkat and KM-3, EP2 receptors seem to play, if any, only a secondary role for the PGE2-mediated cAMP formation in U-937 cells [7].

Biological context of AH23848

• AH23848 is a potent thromboxane A2-receptor blocker inhibiting platelet aggregation in vitro and in vivo [8].
• In a subsequent study, ovulation was inhibited in a dose-dependent fashion by a reported TXA2 receptor antagonist, AH23848 [9].
• There was no significant difference between the placebo and AH23848 treatment periods in exercise tolerance, the rate-pressure product at angina after exercise testing, the number of ischaemic attacks as determined from 24 hour ambulatory electrocardiograms, the number of attacks of pain, or the number of glyceryl trinitrate tablets consumed [3].
• However, an EP4 receptor antagonist (AH23848) significantly suppressed the level of PGE(2)-induced MUC5AC gene expression and MUC5AC mucin [10].

Anatomical context of AH23848

• 6. The results obtained with both the agonists and the antagonist, AH23848 are therefore consistent with prostanoid-induced contractions of human bronchial smooth muscle being mediated by TP-receptors [11].
• PGE2 increased cAMP formation with an ED50 of 50-100 nM in all cell lines. cAMP formation was inhibited by the EP4R-specific antagonist AH23848 [7].

Associations of AH23848 with other chemical compounds

• 4. The TP-receptor blocking drug, AH23848 (1 microM) antagonized the contractile effects of U-46619, PGD2, PGF2 alpha and 11 beta-PGF2, but had no effect against contractions to carbachol [11].
• The role of thromboxane in the gravid normotensive (CD) and hypertensive (SHR) rat was investigated (by utilizing two thromboxane receptor-blocking drugs, EP092 and AH23848) both at mid-gestation and at term [12].
• This lack of a clinical effect with AH23848 was seen despite a profound inhibition of ex vivo platelet aggregation stimulated by the thromboxane A2-mimetic U-46619 [3].

Gene context of AH23848

• The thromboxane A2 receptor antagonist AH23848 (5 mg kg-1, i.v.) inhibited pressor responses to AA in the autoperfused hindquarters, but potentiated depressor responses to AA (0.125-0.5 mg kg-1) in the whole animal [13].

References