Disease relevance of Lopac-P-2278

• The decrease in ectosolic and cytosolic 5'-nucleotidase activity was inhibited by 8-phenyltheophylline and pertussis toxin, and was mimicked by N6-cyclohexyladenosine, an adenosine A1 receptor agonist [1].
• Preconditioning with 2-minute ischemia tended to limit %IS/AR (%IS/AR, 35.5 +/- 3.5%, n = 9), and that possible protection was abolished by pretreatment with 10 mg/kg 8-phenyltheophylline (8-PT), an ADO receptor antagonist (%IS/AR, 43.9 +/- 5.8%, n = 9) [2].
• The blockade of adenosine receptors with 8 phenyltheophylline, before or after the preconditioning tachycardia, reverted its protecting effect but it did not modify infarct size in nonpreconditioned dogs [3].
• The LAD was occluded for 20 or 30 seconds and then released, and reactive hyperemia was observed before and after 8-phenyltheophylline (7.5 mg/kg i.v.) or glibenclamide (200 micrograms/kg into the LAD) infusion [4].
• Hypoxia was repeated before and after 8-phenyltheophylline administration (19.5 mumol.kg-1, intravenously) in seven rabbits, or before and after vehicle injection in five rabbits (time control) [5].

Psychiatry related information on Lopac-P-2278

• Pretest administration of adenosine receptor antagonists theophylline or 8-phenyltheophylline (8-PT) did not alter morphine-induced amnesia [6].

High impact information on Lopac-P-2278

• To test the cause-effect relation between the extent of adenosine release and contractile dysfunction during reperfusion, 8-phenyltheophylline was infused to block adenosine receptors in the methoxamine-treated group [7].
• Neither adenosine deaminase nor 8-phenyltheophylline attenuated the increase in coronary blood flow or the decrease of coronary vascular resistance during exercise [8].
• Analysis of regional blood flows by radioactive microspheres demonstrated that this dose of 8-phenyltheophylline in cirrhotic rats significantly increased portal tributary vascular resistance by 60% and decreased portal tributary blood flow by 26% [9].
• 8-phenyltheophylline did not affect cardiac output, arterial pressure or any other extrasplanchnic hemodynamic variables in cirrhotic rats [9].
• A control group (n = 10) was compared with a group (n = 10) where adenosine receptors were blocked by 8-phenyltheophylline (7.5 mg.kg-1 i.v.) prior to a 10 min occlusion of the left anterior descending coronary artery [10].

Chemical compound and disease context of Lopac-P-2278

• They were studied under anaesthesia while breathing 12% O2 and during acute hypoxia (breathing 8% O2 for 5 min) before and after addition of the adenosine receptor antagonist 8-phenyltheophylline (8-PT, 10 mg kg-1) [11].
• 1. Previous studies have shown that 8-phenyltheophylline (8-PT), a non-selective antagonist at adenosine A1- and A2-receptors, can ameliorate the severity of glycerol-induced acute renal failure (ARF) in the rat [12].
• RESULTS: 8-Phenyltheophylline abolished hypoxia-induced bradycardia and hypertension and produced a nearly 5-fold greater rise in fetal plasma concentrations of corticotropin and approximately a 3-fold greater increase in plasma cortisol levels [13].
• Since the doses of Hoe 140 and 8-phenyltheophylline are sufficient to block the infarct size-limiting effect of preconditioning, the present results suggest that there is a dissociation between the suppression of adenine nucleotide degradation during ischemia by preconditioning and the enhancement of myocardial resistance against infarction [14].
• In six rat groups (half fasted and half with intrajejunal bile-oleate solutions), hyperemia parameters were determined before and after administration of either adenosine deaminase (ADA) or two adenosine receptor antagonists, namely 8-phenyltheophylline (8-PT) and 1,3-dipropyl-7-methylxanthine (DPMX) [15].

Biological context of Lopac-P-2278

• 4. The adenosine antagonist 8-phenyltheophylline (8-PT; 5 microM) inhibited the vasodilatation induced by dipyridamole by 88 +/- 10% [16].
• Administration of 8-phenyltheophylline reduced the effects of hypoxia on spontaneous heart rate and vagal bradycardia: heart rate decreased by 14.2(7.8) beats.min-1 and vagal negative chronotropic effect increased from -32.2(2.1) to -39.3(3.7) beats.min-1, ie, a potentiation of 21.5(10)% [5].
• This effect of N6(L-phenylisopropyl)adenosine was evident by 2 min, had an IC50 of 200 nM, and was prevented by the adenosine receptor antagonist 8-phenyltheophylline [17].
• Coronary blood flow, myocardial oxygen consumption, heart rate, and aortic pressure were measured at rest and during graded treadmill exercise with and without adenosine receptor blockade with either 8-phenyltheophylline (8-PT) or 8-p-sulfophenyltheophylline (8-PST) [18].
• All these responses were antagonized by 8-phenyltheophylline, which suggests that temperature-sensitive vasoconstrictions were mediated by A1 receptors [19].

Anatomical context of Lopac-P-2278

• To explore a possible role for adenosine in the pathogenesis of the splanchnic hyperemia of cirrhosis, we administered 8-phenyltheophylline, a specific adenosine receptor antagonist, to rats with biliary cirrhosis caused by bile duct ligation and to control sham-operated rats [9].
• 6. 8-Phenyltheophylline (5-20 microM) applied to the vas deferens antagonized the conditioning stimulation-induced depression in both the pelvic plexus-vas deferens and the de-ganglionated preparations [20].
• In cellular systems provided with activatory (Ra-site) receptors for adenosine, such as rat cerebral microvessels and rat liver plasma membranes, the adenosine-receptor antagonist 8-phenyltheophylline (10 microM) significantly decreased adenylate cyclase activity if ATP was the substrate and only if GTP was present [21].
• Likewise, the blockade of adenosine receptors with 8-phenyltheophylline, given systemically or as a bolus injection administered directly into the hindlimb circulation during moderate exercise, did not attenuate the hindlimb blood flow response [22].
• This component of transport inhibition could be attributed to the antagonistic effect of methylxanthines at the fat cell A1-adenosine receptor since it was also seen with 8-phenyltheophylline [23].

Associations of Lopac-P-2278 with other chemical compounds

• Dopamine synthesis rate was decreased by the addition of either adenosine deaminase or 8-phenyltheophylline, an adenosine receptor blocker, and was increased by the addition of 2-chloroadenosine [24].
• Stimulation by F (controls) and F plus CA (ADA treated) in cortex slices was significantly inhibited by 200 microM caffeine (CAF) and by 10 microM 8-phenyltheophylline. cAMP accumulation in ADA-treated cortex slices stimulated with CA at concentrations from 5 to 100 microM was markedly enhanced by 1 microM F [25].
• The selective adenosine A2a-receptor antagonist aminophenol (ZM 241385) and the nonselective antagonist 8-phenyltheophylline (8-PT) inhibited these effects [26].
• The decrease could be linked to the decline in cytosolic Pi: both changes were prevented by the adenosine kinase inhibitor 5-iodotubercidin, whereas they were not affected by ibuprofen or 8-phenyltheophylline, and were not reproduced by non-metabolized adenosine analogues [27].
• The potency of 8-phenyltheophylline, theophylline and enprofylline as adenosine antagonists was assessed in vitro, using the guinea-pig isolated atrium, and in vivo, using the anaesthetized dog [28].

Gene context of Lopac-P-2278

• 6. The potency and specificity of 8-phenyltheophylline as an inhibitor of human hepatic CYP1A2 indicate that the compound may be useful as a chemical inhibitor of this enzyme for further in vitro studies [29].
• The post-ATP facilitation could be prevented by the adenosine A1 receptor antagonists 8-phenyltheophylline or 1,3-dipropyl-8-cyclopentyltheophylline (50 nM), or superfusion of adenosine deaminase [30].
• Pretreatment with a P1-purinoceptor antagonist, 8-phenyltheophylline (10 microM) or P2X-purinoceptor antagonist, Evans blue (10 microM) did not influence the relaxations to EFS and exogenously added ATP [31].
• Preincubation with adenosine deaminase (ADA, 5.0 U/ml) or with 8-phenyltheophylline (8-PT, 10(-6) to 10(-4) M) increased, rather than blocked the vasorelaxant effect of acetate [32].
• A1R antagonists, 8-cyclolentyl-1,3-dipropylxanthine and 8-phenyltheophylline, did not inhibit the hypoxic response of KDR mRNA at A1R inhibitory concentrations but did inhibit the response at A2R effective doses (P = 0.001) [33].

Analytical, diagnostic and therapeutic context of Lopac-P-2278

• Adenosine release during reperfusion was augmented (22.7 +/- 1.9 nmol.100 g-1.min-1, p less than 0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia [34].
• In four dogs, 8-phenyltheophylline (10 microM, superfusion for 30 min) did not affect the metabolic dilation of arterioles (15.3 +/- 2.0% before and 16.4 +/- 3.8% after treatment; 84.3 +/- 11.0 microm at control, n = 8) [35].
• The present experiments indicate that this enhancement is comparable with that produced by perfusion with an adenosine antagonist, 8-phenyltheophylline, and that superfusion with this compound or adenosine deaminase precludes any enhancement of potential size in low magnesium solutions [36].
• We investigated the involvement of adenosine in ischemic preconditioning (IPC) by the unspecific antagonist, 8-phenyltheophylline (8-PT) [37].
• Intraportal administration of an adenosine receptor antagonist (8-phenyltheophylline (8-PT), 3 mg kg(-1) bolus injection followed by 0.05 mg kg(-1) min(-1) continuous infusion), as well as liver or kidney denervation, abolished adenosine-induced inhibition [38].

References