Detail of "134308-13-7"

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Determination of the catechol-O-methyltransferase inhibitor Ro 40-7592 in human plasma by high-performance liquid chromatography with coulometric detection

Determination of the catechol-O-methyltransferase inhibitor Ro 40-7592 in human plasma by high-performance liquid chromatography with coulometric detection. Timm, U.; Erdin, R. (Pharma Div., F. Hoffmann-La Roche Ltd., Basel CH-4002, Switz.). J. Chromatogr., 593(1-2), 63-8 (English) 1992. CODEN: JOCRAM. ISSN: 0021-9673. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A sensitive and specific HPLC method has been developed to measure the catechol-O-methyltransferase (COMT) inhibitor 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone (Ro 40-7592) in human plasma. The compd. and the internal std. were extd. from plasma at pH 2 with n-Bu chloride-Et acetate (, vol./vol.). The ext. was chromatographed on a reversed-phase column (Hypersil ODS, 5 mm) using a mixt. of phosphate buffer (0.05M, pH 2), methanol and THF (:5, vol./vol./v) as the mobile phase. Long-retained components were removed from the system by means of a simple column-switching system. Quantification of the catechol-O-methyltransferase inhibitor was performed by means of coulometric detection (0.15 V). The limit of quantification wa about 1 ng/mL, using a 1-mL specimen of plasma. The recovery from human plasma was >88%. The mean inter-assay precision was 5.3% in the range 2.5-1000 ng/mL. Linearity of the std. curve wa obtained in the concn. range 2.In this experiment, several chemicals are used like 134308-13-7 5-500 ng/mL. The catechol-O-methyltransferase inhibitor was stable in human plasma when stored for six months at -20° and for 24 h at room temp. The practicability of the new method was demonstrated by the anal. of more than 400 plasmid samples from a tolerance study performed in human volunteers. .

Different in vivo properties of three new inhibitors of catechol O-methyltransferase in the rat

Different in vivo properties of three new inhibitors of catechol O-methyltransferase in the rat. Mannisto, Pekka T.; Tuomainen, Paivi; Tuominen, Raimo K. (Dep. Pharmacol. Toxicol., Univ. Helsinki, Helsinki SF-00170, Finland). Br. J. Pharmacol., 105(3), 569-74 (English) 1992. CODEN: BJPCBM. ISSN: 0007-1188. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The authors compared three new catechol O-methyltransferase (COMT) inhibitors (OR-611, Ro 40-7592 and CGP 28014; 10 and 30 mg kg-1, i.p.) in male rats given levodopa (L-DOPA, 50 mg kg-1, i.p.) and carbidopa ((-)-L-a-Me dopa, 50 mg kg-1, i.p. 134308-13-7 and 300-48-1 which are cas registry numbers are also used here.). In some studies pretreatment with pargyline (80 mg kg-1, i.p.) was used to block the function of monoamine oxidase (MAO). Decreases of hypothalamic and striatal 3-O-methyl-dopa (3-OMD) levels were used as measures of the inhibition of peripheral COMT. The inhibition of brain COMT activity was estd. by decreases of hypothalamic and striatal homovanillic acid (HVA) and 3-methoxytyramine (3-MT; after pargyline) levels. The three COMT inhibitors studied had different individual characteristics. OR-611 was primarily a peripherally acting COMT inhibitor, decreasing 3-OMD levels in the striatum (to 31-52%) and in the hypothalamus (to 16-27%) both in the control and pargyline-treated animals at 1 and 3 h. It did not have any effect on brain HVA and 3-MT. Ro 40-7592 was a broad spectrum COMT inhibitor decreasing striatal and hypothalamic 3-OMD (always to <30%), HVA (to <50%) and 3-MT levels (to <23%) significantly both at 1 and 3 h. It was more potent than OR-611. CGP 28014 functioned as a weak COMT inhibitor in the periphery inhibiting 3-OMD formation only at 3 h. In contrast, it was fairly potent in decreasing the brain HVA and 3-MT levels at 1 h (to 37-22% and 42-35% in the striatum, and to 57-33% and 64-35% in the hypothalamus, resp.) but not at 3 h. Since CGP 28014, unlike OR-611 and Ro 40-7592, did not generally increase the brain DOPA, dopamine or DOPAC levels, it was not a typical COMT inhibitor. .