caa a22 4500 469078162 CHVBK 20180323132941.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF00173538 doi (NATIONALLICENCE)springer-10.1007/BF00173538 Biochemical and pharmacological properties of a peripherally acting catechol-O-methyltransferase inhibitor entacapone [Elektronische Daten] [Erkki Nissinen, Inge-Britt Linden, Eija Schultz, Pentti Pohto] Summary: Entacapone, OR-611, was found to be a potent peripherally acting inhibitor of catechol-O-methyl-transferase (COMT). IC50 values of 10 nmol/1 and 160 nmol/1 were obtained for rat duodenum and liver-soluble COMT, respectively. There were no effects on other catecholamine metabolizing enzymes. Entacapone showed reversible, tight-binding type of inhibition of soluble rat liver COMT with a K; value of 14 nmol/1 and it also caused 50% inhibition of rat duodenal, erythrocyte, liver and striatal COMT activity 1 h after oral dosing with 1.1, 5.4, 6.7 and 24.2 mg/kg, respectively. However, penetration of entacapone into the brain was poor, since the formation of homovanillic acid (HVA), the O-methyl metabolite of dopamine in the striatum, was not reduced, even after the highest dose of 30 mg/kg. In rat blood serum, the concentration of 3-0-methyldopa (3OMD), the O-methylated product of l-dopa, was reduced in a dose-dependent manner, and the concentration of l-dopa was increased after the administration of entacapone (3 - 30 mg/kg p. o.) together with l-dopa + carbidopa. These changes were reflected, in the striatum, by a significant rise in the dopamine concentration and a reduction in the 30MD concentration. Consequently, when entacapone was added to the treatment with l-dopa + carbidopa, the dose of l-dopa could be lowered from 50 mg/kg to 15 mg/kg in order to produce the same striatal dopamine concentrations as with 50 + 50 mg/kg of l-dopa + carbidopa alone. Springer-Verlag, 1992 Entacapone nationallicence COMT inhibition nationallicence l -dopa nationallicence Parkinsonism nationallicence Nissinen Erkki Orion Farmos-Pharmaceuticals, Orion Research Center, P. O. Box 65, SF-02101, Espoo, Finland aut Linden Inge-Britt Orion Farmos-Pharmaceuticals, Orion Research Center, P. O. Box 65, SF-02101, Espoo, Finland aut Schultz Eija Orion Farmos-Pharmaceuticals, Orion Research Center, P. O. Box 65, SF-02101, Espoo, Finland aut Pohto Pentti Orion Farmos-Pharmaceuticals, Orion Research Center, P. O. Box 65, SF-02101, Espoo, Finland aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 262-266 0028-1298 346:3<262 1992 346 210 https://doi.org/10.1007/BF00173538 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00173538 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nissinen Erkki Orion Farmos-Pharmaceuticals, Orion Research Center, P. O. Box 65, SF-02101, Espoo, Finland aut NATIONALLICENCE 700 1- Linden Inge-Britt Orion Farmos-Pharmaceuticals, Orion Research Center, P. O. Box 65, SF-02101, Espoo, Finland aut NATIONALLICENCE 700 1- Schultz Eija Orion Farmos-Pharmaceuticals, Orion Research Center, P. O. Box 65, SF-02101, Espoo, Finland aut NATIONALLICENCE 700 1- Pohto Pentti Orion Farmos-Pharmaceuticals, Orion Research Center, P. O. Box 65, SF-02101, Espoo, Finland aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 262-266 0028-1298 346:3<262 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer