;PMID: 9248786 ;source_file_1785.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..58] = [t:0..58] ;1)sentence:[e:64..139] = [t:64..139] ;2)section:[e:143..188] = [t:143..188] ;3)section:[e:192..283] = [t:192..283] ;4)sentence:[e:287..477] = [t:287..477] ;5)sentence:[e:478..711] = [t:478..711] ;6)sentence:[e:712..962] = [t:712..962] ;7)sentence:[e:963..1104] = [t:963..1104] ;8)sentence:[e:1105..1162] = [t:1105..1162] ;9)sentence:[e:1163..1325] = [t:1163..1325] ;10)sentence:[e:1326..1472] = [t:1326..1472] ;11)sentence:[e:1473..1586] = [t:1473..1586] ;12)sentence:[e:1588..1715] = [t:1588..1715] ;13)section:[e:1719..1763] = [t:1719..1763] ;section 0 Span:0..58 ;Eur J Drug Metab Pharmacokinet. 1997 Apr-Jun;22(2):165-71. (SEC (FRAG (NNP:[0..3] Eur) (NNP:[4..5] J) (NNP:[6..10] Drug) (NNP:[11..16] Metab) (NNP:[17..30] Pharmacokinet) (.:[30..31] .) (CD:[32..36] 1997) (NNP:[37..40] Apr) (::[40..41] -) (CD:[41..47] Jun;22) (-LRB-:[47..48] -LRB-) (CD:[48..49] 2) (-RRB-:[49..50] -RRB-) (CD:[50..54] :165) (::[54..55] -) (CD:[55..57] 71) (.:[57..58] .))) ;sentence 1 Span:64..139 ;Interaction of chlormezanone with rat liver microsomes and its degradation. ;[79..92]:substance:"chlormezanone" (SENT (NP-HLN (NP (NP (NN:[64..75] Interaction)) (PP (IN:[76..78] of) (NP (NN:[79..92] chlormezanone))) (PP (IN:[93..97] with) (NP (NN:[98..101] rat) (NN:[102..107] liver) (NNS:[108..118] microsomes)))) (CC:[119..122] and) (NP (PRP$:[123..126] its) (NN:[127..138] degradation)) (.:[138..139] .))) ;section 2 Span:143..188 ;Klinger W, Oelschlager H, Karge E, Rothley D. (SEC (FRAG (NNP:[143..150] Klinger) (NNP:[151..152] W) (,:[152..153] ,) (NNP:[154..165] Oelschlager) (NNP:[166..168] H,) (NNP:[169..174] Karge) (NNP:[175..176] E) (,:[176..177] ,) (NNP:[178..185] Rothley) (NNP:[186..188] D.))) ;section 3 Span:192..283 ;Institut fur Pharmakologie und Toxikologie, Friedrich-Schiller-Universitat, ;Jena, Germany. (SEC (FRAG (NNP:[192..200] Institut) (NN:[201..204] fur) (NNP:[205..218] Pharmakologie) (VBD:[219..222] und) (NNP:[223..234] Toxikologie) (,:[234..235] ,) (NNP:[236..254] Friedrich-Schiller) (NNP:[254..266] -Universitat) (,:[266..267] ,) (NNP:[269..273] Jena) (,:[273..274] ,) (NNP:[275..282] Germany) (.:[282..283] .))) ;sentence 4 Span:287..477 ;Chlormezanone binds to oxidized cytochrome P450 in rat liver microsomes with ;a binding curve according to type I like hexobarbital but less pronounced ;and with a general shift to the left. ;[287..300]:substance:"Chlormezanone" ;[319..334]:cyp450:"cytochrome P450" ;[406..418]:substance:"hexobarbital" (SENT (S (NP-SBJ (NN:[287..300] Chlormezanone)) (VP (VBZ:[301..306] binds) (PP-CLR (TO:[307..309] to) (NP (VBN:[310..318] oxidized) (NN:[319..329] cytochrome) (NN:[330..334] P450))) (PP-LOC (IN:[335..337] in) (NP (NN:[338..341] rat) (NN:[342..347] liver) (NNS:[348..358] microsomes))) (PP (IN:[359..363] with) (NP (NP (DT:[364..365] a) (VBG:[367..374] binding) (NN:[375..380] curve)) (VP (VBG:[381..390] according) (PP (TO:[391..393] to) (NP (NN:[394..398] type) (CD:[399..400] I)))) (UCP (PP (IN:[401..405] like) (NP (NN:[406..418] hexobarbital))) (CC:[419..422] but) (UCP (ADJP (RBR:[423..427] less) (JJ:[428..438] pronounced)) (CC:[439..442] and) (PP (IN:[443..447] with) (NP (NP (DT:[449..450] a) (JJ:[451..458] general) (NN:[459..464] shift)) (PP (TO:[465..467] to) (NP (DT:[468..471] the) (NN:[472..476] left)))))))))) (.:[476..477] .))) ;sentence 5 Span:478..711 ;Ethylmorphine N-demethylation, ethoxycoumarin and ethoxyresorufin ;O-deethylation are inhibited by chlormezanone in mM concentrations only ;whereas pentoxyresorufin O-depentylation is inhibited by about 50% in microM ;concentrations. ;[478..491]:substance:"Ethylmorphine" ;[509..523]:substance:"ethoxycoumarin" ;[529..544]:substance:"ethoxyresorufin" ;[577..590]:substance:"chlormezanone" ;[594..596]:quantitative-units:"mM" ;[626..642]:substance:"pentoxyresorufin" ;[682..685]:quantitative-value:"50%" ;[689..695]:quantitative-units:"microM" (SENT (S (NP-SBJ-2 (NP (NN:[478..491] Ethylmorphine) (NN:[492..507] N-demethylation)) (,:[507..508] ,) (NP (NN:[509..523] ethoxycoumarin) (NML-3 (-NONE-:[523..523] *P*))) (CC:[524..527] and) (NP (NN:[529..544] ethoxyresorufin) (NML-3 (NN:[545..559] O-deethylation)))) (VP (VBP:[560..563] are) (VP (VBN:[564..573] inhibited) (NP-2 (-NONE-:[573..573] *)) (PP (IN:[574..576] by) (NP-LGS (NN:[577..590] chlormezanone))) (PP (IN:[591..593] in) (NP (NN:[594..596] mM) (NNS:[598..612] concentrations))) (ADVP (RB:[613..617] only)))) (SBAR-ADV (IN:[618..625] whereas) (S (NP-SBJ-1 (NN:[626..642] pentoxyresorufin) (NN:[643..658] O-depentylation)) (VP (VBZ:[659..661] is) (VP (VBN:[662..671] inhibited) (NP-1 (-NONE-:[671..671] *)) (PP (IN:[672..674] by) (NP-EXT (QP (RB:[676..681] about) (CD:[682..684] 50)) (NN:[684..685] %))) (PP (IN:[686..688] in) (NP (NN:[689..695] microM) (NNS:[696..710] concentrations))))))) (.:[710..711] .))) ;sentence 6 Span:712..962 ;Luminol and lucigenin amplified chemiluminescence indicating the formation ;of reactive oxygen species was not influenced in concentration ranges ;between mM and microM, whereas NADPH/Fe stimulated lipid peroxidation showed ;a tendency of inhibition. ;[712..719]:substance:"Luminol" ;[724..733]:substance:"lucigenin" ;[800..814]:substance:"oxygen species" ;[867..869]:quantitative-units:"mM" ;[874..880]:quantitative-units:"microM" ;[890..895]:substance:"NADPH" ;[896..898]:substance:"Fe" ;[911..916]:substance:"lipid" (SENT (S (NP-SBJ-1 (NP (ADJP (NML (NN:[712..719] Luminol) (CC:[720..723] and) (NN:[724..733] lucigenin)) (VBD:[734..743] amplified)) (NN:[745..762] chemiluminescence)) (VP (VBG:[763..773] indicating) (NP (NP (DT:[774..777] the) (NN:[778..787] formation)) (PP (IN:[788..790] of) (NP (JJ:[791..799] reactive) (NN:[800..806] oxygen) (NN:[807..814] species)))))) (VP (VBD:[815..818] was) (RB:[819..822] not) (VP (VBN:[824..834] influenced) (NP-1 (-NONE-:[834..834] *)) (PP (IN:[835..837] in) (NP (NP (NN:[838..851] concentration) (NNS:[852..858] ranges)) (PP (IN:[859..866] between) (NP (NN:[867..869] mM) (CC:[870..873] and) (NN:[874..880] microM))))))) (,:[880..881] ,) (SBAR-ADV (IN:[882..889] whereas) (S (NP-SBJ (ADJP (NML (NN:[890..895] NADPH) (SYM:[895..896] /) (NN:[896..898] Fe)) (VBN:[900..910] stimulated)) (NN:[911..916] lipid) (NN:[917..929] peroxidation)) (VP (VBD:[930..936] showed) (NP (NP (DT:[937..938] a) (NN:[939..947] tendency)) (PP (IN:[948..950] of) (NP (NN:[951..961] inhibition))))))) (.:[961..962] .))) ;sentence 7 Span:963..1104 ;But scavenger activity could not be demonstrated: the zymosan stimulated ;chemiluminescence of whole blood was not influenced significantly. ;[1018..1025]:substance:"zymosan" (SENT (S (S (ADVP (CC:[963..966] But)) (NP-SBJ-2 (NN:[967..976] scavenger) (NN:[978..986] activity)) (VP (MD:[987..992] could) (RB:[993..996] not) (VP (VB:[997..999] be) (VP (VBN:[1000..1012] demonstrated) (NP-2 (-NONE-:[1012..1012] *)))))) (::[1012..1013] :) (S (NP-SBJ-1 (NP (DT:[1014..1017] the) (ADJP (NN:[1018..1025] zymosan) (VBN:[1026..1036] stimulated)) (NN:[1037..1054] chemiluminescence)) (PP (IN:[1055..1057] of) (NP (JJ:[1059..1064] whole) (NN:[1065..1070] blood)))) (VP (VBD:[1071..1074] was) (RB:[1075..1078] not) (VP (VBN:[1079..1089] influenced) (NP-1 (-NONE-:[1089..1089] *)) (ADVP-MNR (RB:[1090..1103] significantly))))) (.:[1103..1104] .))) ;sentence 8 Span:1105..1162 ;The degradation process of chlormezanone was elucidated. ;[1133..1146]:substance:"chlormezanone" (SENT (S (NP-SBJ-1 (NP (DT:[1105..1108] The) (NN:[1109..1120] degradation) (NN:[1121..1128] process)) (PP (IN:[1129..1131] of) (NP (NN:[1133..1146] chlormezanone)))) (VP (VBD:[1147..1150] was) (VP (VBN:[1151..1161] elucidated) (NP-1 (-NONE-:[1161..1161] *)))) (.:[1161..1162] .))) ;sentence 9 Span:1163..1325 ;The first step involves ring opening by chemical hydrolysis with subsequent ;formation of an unstable acylhalfaminal which is the source of ;4-chlorobenzaldehyde. ;[1203..1211]:substance:"chemical" ;[1265..1279]:substance:"acylhalfaminal" ;[1304..1324]:substance:"4-chlorobenzaldehyde" (SENT (S (NP-SBJ (DT:[1163..1166] The) (JJ:[1167..1172] first) (NN:[1173..1177] step)) (VP (VBZ:[1178..1186] involves) (NP (NP (NN:[1187..1191] ring) (NN:[1192..1199] opening)) (PP (IN:[1200..1202] by) (NP (JJ:[1203..1211] chemical) (NN:[1213..1223] hydrolysis))) (PP (IN:[1224..1228] with) (NP (NP (JJ:[1229..1239] subsequent) (NN:[1240..1249] formation)) (PP (IN:[1250..1252] of) (NP (NP (DT:[1253..1255] an) (JJ:[1256..1264] unstable) (NN:[1265..1279] acylhalfaminal)) (SBAR (WHNP-1 (WDT:[1280..1285] which)) (S (NP-SBJ-1 (-NONE-:[1285..1285] *T*)) (VP (VBZ:[1286..1288] is) (NP-PRD (NP (DT:[1289..1292] the) (NN:[1294..1300] source)) (PP (IN:[1301..1303] of) (NP (NN:[1304..1324] 4-chlorobenzaldehyde))))))))))))) (.:[1324..1325] .))) ;sentence 10 Span:1326..1472 ;This aldehyde undergoes enzymatically controlled oxidation to ;4-chlorobenzoic acid which is the parent compound of following phase II ;reactions. ;[1331..1339]:substance:"aldehyde" ;[1389..1409]:substance:"4-chlorobenzoic acid" ;[1430..1438]:substance:"compound" (SENT (S (NP-SBJ (DT:[1326..1330] This) (NN:[1331..1339] aldehyde)) (VP (VBZ:[1340..1349] undergoes) (NP (NP (ADJP (RB:[1350..1363] enzymatically) (VBN:[1364..1374] controlled)) (NN:[1376..1385] oxidation)) (PP (TO:[1386..1388] to) (NP (NP (JJ:[1389..1404] 4-chlorobenzoic) (NN:[1405..1409] acid)) (SBAR (WHNP-1 (WDT:[1410..1415] which)) (S (NP-SBJ-1 (-NONE-:[1415..1415] *T*)) (VP (VBZ:[1416..1418] is) (NP-PRD (NP (DT:[1419..1422] the) (NN:[1423..1429] parent) (NN:[1430..1438] compound)) (PP (IN:[1439..1441] of) (NP (VBG:[1442..1451] following) (NML (NN:[1453..1458] phase) (CD:[1459..1461] II)) (NNS:[1462..1471] reactions))))))))))) (.:[1471..1472] .))) ;sentence 11 Span:1473..1586 ;The second degradation product is ;2-carboxyethane-sulfinic-acid-N-methylamide, which is hydrolyzed very ;quickly. ;[1496..1503]:substance:"product" ;[1508..1551]:substance:"2-carboxyethane-sulfinic-acid-N-methylamide" (SENT (S (NP-SBJ (DT:[1473..1476] The) (JJ:[1477..1483] second) (NN:[1484..1495] degradation) (NN:[1496..1503] product)) (VP (VBZ:[1504..1506] is) (NP-PRD (NP (NN:[1508..1551] 2-carboxyethane-sulfinic-acid-N-methylamide)) (,:[1551..1552] ,) (SBAR (WHNP-1 (WDT:[1553..1558] which)) (S (NP-SBJ-1 (-NONE-:[1558..1558] *T*)) (VP (VBZ:[1559..1561] is) (VP (VBN:[1562..1572] hydrolyzed) (NP-1 (-NONE-:[1572..1572] *)) (ADVP-MNR (RB:[1573..1577] very) (RB:[1578..1585] quickly)))))))) (.:[1585..1586] .))) ;sentence 12 Span:1588..1715 ;Neither oxidation of the sulfinic acid or its N-methylamide derivative could ;be observed nor N-demethylation of chlormezanone. ;[1613..1626]:substance:"sulfinic acid" ;[1634..1658]:substance:"N-methylamide derivative" ;[1701..1714]:substance:"chlormezanone" (SENT (S (CC:[1588..1595] Neither) (S (NP-SBJ-1 (NP (NN:[1596..1605] oxidation)) (PP (IN:[1606..1608] of) (NP (NP (DT:[1609..1612] the) (JJ:[1613..1621] sulfinic) (NN:[1622..1626] acid)) (CC:[1627..1629] or) (NP (PRP$:[1630..1633] its) (NN:[1634..1647] N-methylamide) (NN:[1648..1658] derivative))))) (VP (MD:[1659..1664] could) (VP (VB:[1665..1667] be) (VP (VBN:[1669..1677] observed) (NP-1 (-NONE-:[1677..1677] *)))))) (CC:[1678..1681] nor) (S (NP-SBJ (NP (NN:[1682..1697] N-demethylation)) (PP (IN:[1698..1700] of) (NP (NN:[1701..1714] chlormezanone)))) (VP (-NONE-:[1714..1714] *?*))) (.:[1714..1715] .))) ;section 13 Span:1719..1763 ;PMID: 9248786 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1719..1723] PMID) (::[1723..1724] :) (CD:[1725..1732] 9248786) (NN:[1733..1734] -LSB-) (NNP:[1734..1740] PubMed) (::[1741..1742] -) (NN:[1743..1750] indexed) (IN:[1751..1754] for) (NNP:[1755..1763] MEDLINE-RSB-)))