Disease relevance of U 0521

• The accumulation of ISO when catechol-O-methyltransferase (COMT) (EC 2.1.1.6) was inhibited by 3',4'-dihydroxy-2-methylpropiophenone (U-0521) was decreased by ischemia to about 50% of the control value [1].

High impact information on U 0521

• The most active compounds were more than 1000 times more potent (IC50 = 3-6 nM) in vitro than the known COMT inhibitor, 3',4'-dihydroxy-2-methylpropiophenone (U 0521, IC50 = 6000 nM) [2].
• The drug U-0521, which has been used as an inhibitor of catechol-O-methyltransferase (COMT), was also found to be an inhibitor of tyrosine hydroxylase [3].
• Experiments were performed to determine the effect of pretreatment with 3',4'-dihydroxy-2-methyl-propiophenone (U-0521), a competitive inhibitor of COMT, on [18F]DOPA metabolism in the carbidopa-pretreated hooded rat [4].
• Increased decarboxylation of [18F]DOPA in the striatum of U-0521-treated rats resulted in heightened radiocontrast between striatum and other cerebral tissues [4].
• The effects of U-0521 and ascorbate on 2-OH-E2-stimulated progesterone production in vitro was also examined [5].

Biological context of U 0521

• The inhibition of catechol-O-methyltransferase by U-0521 caused a decrease of NMN and OMDA during the spontaneous outflow, and a shift from O-methylation to deamination of NE [6].
• After the five week treatment period, the blood pressure of the U-0521 treated animals escalated rapidly to match the saline treated controls [7].
• 1. The influence of catechol-O-methyltransferase inhibitor U-0521 on isotonic contraction of isolated rat vas deferens was examined to determine optimal concentration and nonspecific effects [8].

Anatomical context of U 0521

• Both cortisol and U-0521 appear to be extraneuronal uptake inhibitors and inhibitors of catechol-O-methyltransferase in coronary arteries [9].
• Effect of 3',4'-dihydroxy-2-methyl-propriophenone (U-0521) on catechol-O-methyltransferase activity and on DOPA accumulation in rat red blood cells and corpus striatum [10].
• The effects of the catechol-O-methyltransferase (COMT) inhibitor 3',4'-dihydroxy-2-methyl-propriophenone (U-0521) were studied in red blood cells (RBC) and corpus striatum in the rat [10].
• The adrenergic nerve endings of the rat vas deferens were loaded with 3H-(-)-noradrenaline; COMT was inhibited by the presence of 10 mumol/l U-0521, and all experiments were carried out with calcium-free solution [11].
• Silver grain density, especially over the smooth muscle, was markedly increased by U-0521 and decreased by cortexone [12].

Associations of U 0521 with other chemical compounds

• It is concluded that 3H-MPP+ is efficiently taken up by rat hepatocytes by a carrier-mediated mechanism sensitive to catecholamines, decynium22 and cyanane863, and to the enzyme inhibitors pargyline, Ro 01-2812 and U-0521 [13].
• Cocaine (12 microM) enhanced the alpha-effect elicited by electrical stimulation 2.8 +/- 0.2 (n = 7) times but did not change the beta-effect, whereas U-0521 (50 microM) enhanced the beta-effect 3.4 +/- 0.2 (n = 8) times without changing the alpha-effect [14].
• Catechol-O-methyltransferase inhibition by U-0521 increases striatal utilization of levodopa [15].
• Segments of cat, rat or rabbit trachea, dog coronary artery or cat atria were incubated in isoprenaline, in the presence of U-0521 (100 mumol l-1) to inhibit catechol-O-methyltransferase [16].
• Rabbit aortic strips (nerve-free, reserpine-pretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1mM U-0521) were exposed to 1.18 muM labelled (-)- or (+)noradrenaline for 30 min [17].

Gene context of U 0521

• In these experiments, 12 mumol/l cocaine (to inhibit uptake1), 41 mumol/l hydrocortisone (to reduce uptake2) and 50 mumol/l U-0521 (to inhibit COMT) were present during the perifusion [18].
• Altered metabolism of [18F]-6-fluorodopa in the hooded rat following inhibition of catechol-O-methyltransferase with U-0521 [4].
• U-0521, a potent COMT inhibitor, was shown, after i.p. injection, to effectively block the accumulation of OMD in the plasma and to enhance L-DOPA metabolism in rat brain [19].

Analytical, diagnostic and therapeutic context of U 0521

• During electric stimulation, U-0521 markedly decreased the formation of NMN and OMDA and caused an increase in outflow of NE [6].
• Denervation, reserpine and cortex-one blocked the accumulation of adrenaline, whereas U-0521 was the only drug to increase accumulation of adrenaline [20].

References