;PMID: 8272405
;source_file_1735.mrg
;Release 0.9 of PennBioIE
;Funded by NSF ITR EIA-0205448

;0)section:[e:0..34] = [t:0..34]
;1)sentence:[e:40..165] = [t:40..165]
;2)section:[e:169..206] = [t:169..206]
;3)section:[e:210..351] = [t:210..351]
;4)sentence:[e:355..422] = [t:355..422]
;5)sentence:[e:423..502] = [t:423..502]
;6)sentence:[e:503..651] = [t:503..651]
;7)sentence:[e:652..837] = [t:652..837]
;8)sentence:[e:838..975] = [t:838..975]
;9)sentence:[e:976..1082] = [t:976..1082]
;10)sentence:[e:1083..1152] = [t:1083..1152]
;11)sentence:[e:1153..1271] = [t:1153..1271]
;12)section:[e:1275..1319] = [t:1275..1319]

;section 0 Span:0..34
;Pharm Res. 1993 Oct;10(10):1442-5.
(SEC
  (FRAG (NNP:[0..5] Pharm) (NNP:[6..9] Res) (.:[9..10] .) (CD:[11..15] 1993)
        (CC:[16..23] Oct;10-LRB-) (CD:[23..25] 10) (NN:[25..26] -RRB-)
        (::[26..27] :) (CD:[27..33] 1442-5) (.:[33..34] .)))

;sentence 1 Span:40..165
;Pharmacokinetics, mass balance, and induction potential of a novel GABA
;uptake  inhibitor, CI-966 HCl, in laboratory animals.
;[107..111]:substance:"GABA"
;[120..129]:substance:"inhibitor"
;[131..141]:substance:"CI-966 HCl"
(SENT
  (NP-HLN
    (NP
      (NP (NNS:[40..56] Pharmacokinetics))
      (,:[56..57] ,)
      (NP (NN:[58..62] mass) (NN:[63..70] balance))
      (,:[70..71] ,) (CC:[72..75] and)
      (NP (NN:[76..85] induction) (NN:[86..95] potential)))
    (PP (IN:[96..98] of)
      (NP
        (NP (DT:[99..100] a) (JJ:[101..106] novel)
          (NML (NN:[107..111] GABA) (NN:[112..118] uptake))
          (NN:[120..129] inhibitor))
        (,:[129..130] ,)
        (NP (NN:[131..137] CI-966) (NN:[138..141] HCl))))
    (,:[141..142] ,)
    (PP-LOC (IN:[143..145] in)
      (NP (NN:[146..156] laboratory) (NNS:[157..164] animals)))
    (.:[164..165] .)))

;section 2 Span:169..206
;Radulovic LL, Bockbrader HN, Chang T.
(SEC
  (FRAG (NNP:[169..178] Radulovic) (NNP:[179..181] LL) (,:[181..182] ,)
        (NNP:[183..193] Bockbrader) (NNP:[194..196] HN) (,:[196..197] ,)
        (NNP:[198..203] Chang) (NNP:[204..206] T.)))

;section 3 Span:210..351
;Pharmacokinetics/Drug Metabolism Department, Parke-Davis Pharmaceutical
;Research  Division, Warner-Lamber Company, Ann Arbor, Michigan 48105.
(SEC
  (FRAG (NNP:[210..226] Pharmacokinetics) (NNP:[226..227] /)
        (NNP:[227..231] Drug) (NNP:[232..242] Metabolism)
        (NNP:[243..253] Department) (,:[253..254] ,) (NNP:[255..260] Parke)
        (HYPH:[260..261] -) (NNP:[261..266] Davis)
        (NNP:[267..281] Pharmaceutical) (NNP:[282..290] Research)
        (NNP:[292..300] Division) (,:[300..301] ,) (NNP:[302..308] Warner)
        (HYPH:[308..309] -) (NNP:[309..315] Lamber) (NNP:[316..323] Company)
        (,:[323..324] ,) (NNP:[325..328] Ann) (NNP:[329..334] Arbor)
        (,:[334..335] ,) (NNP:[336..344] Michigan) (CD:[345..350] 48105)
        (.:[350..351] .)))

;sentence 4 Span:355..422
;CI-966 exhibits anticonvulsant properties in various animal models.
;[355..361]:substance:"CI-966"
;[371..385]:substance:"anticonvulsant"
(SENT
  (S
    (NP-SBJ (NN:[355..361] CI-966))
    (VP (VBZ:[362..370] exhibits)
      (NP (JJ:[371..385] anticonvulsant) (NNS:[386..396] properties))
      (PP-LOC (IN:[397..399] in)
        (NP (JJ:[400..407] various) (NN:[408..414] animal)
            (NNS:[415..421] models))))
    (.:[421..422] .)))

;sentence 5 Span:423..502
;The drug  acts by inhibiting synaptic uptake of gamma-aminobutyric acid
;(GABA).
;[427..431]:substance:"drug"
;[471..494]:substance:"gamma-aminobutyric acid"
;[496..500]:substance:"GABA"
(SENT
  (S
    (NP-SBJ-1 (DT:[423..426] The) (NN:[427..431] drug))
    (VP (VBZ:[433..437] acts)
      (PP-MNR (IN:[438..440] by)
        (S-NOM
          (NP-SBJ-1 (-NONE-:[440..440] *))
          (VP (VBG:[441..451] inhibiting)
            (NP
              (NP (JJ:[452..460] synaptic) (NN:[461..467] uptake))
              (PP (IN:[468..470] of)
                (NP
                  (NP (JJ:[471..489] gamma-aminobutyric) (NN:[490..494] acid))
                  (NP (-LRB-:[495..496] -LRB-) (NN:[496..500] GABA)
                      (-RRB-:[500..501] -RRB-)))))))))
    (.:[501..502] .)))

;sentence 6 Span:503..651
;Oral  absorption of CI-966 in dogs given 1.39 mg/kg is rapid with a tmax of
;0.7 hr. In  rats given 5 mg/kg oral, a mean tmax of 4.0 hr was observed.
;[523..529]:substance:"CI-966"
;[544..548]:quantitative-value:"1.39"
;[549..554]:quantitative-units:"mg/kg"
;[571..575]:quantitative-name:"tmax"
;[579..582]:quantitative-value:"0.7"
;[583..585]:quantitative-units:"hr"
;[602..603]:quantitative-value:"5"
;[604..609]:quantitative-units:"mg/kg"
;[623..627]:quantitative-name:"tmax"
;[631..634]:quantitative-value:"4.0"
;[635..637]:quantitative-units:"hr"
(SENT
  (S
    (NP-SBJ
      (NP (JJ:[503..507] Oral) (NN:[509..519] absorption))
      (PP (IN:[520..522] of)
        (NP (NN:[523..529] CI-966)))
      (PP-LOC (IN:[530..532] in)
        (NP
          (NP (NNS:[533..537] dogs))
          (VP (VBN:[538..543] given)
            (NP (-NONE-:[543..543] *))
            (NP
              (NP (CD:[544..548] 1.39) (NN:[549..551] mg))
              (PP (SYM:[551..552] /)
                (NP (NN:[552..554] kg))))))))
    (VP (VBZ:[555..557] is)
      (ADJP-PRD (JJ:[558..563] rapid))
      (PP (IN:[564..568] with)
        (NP
          (NP (DT:[569..570] a) (NN:[571..575] tmax))
          (PP (IN:[576..578] of)
            (NP (CD:[579..582] 0.7) (NN:[583..585] hr))))))
    (.:[585..586] .))
  (S
    (PP-LOC (IN:[587..589] In)
      (NP
        (NP (NNS:[591..595] rats))
        (VP (VBN:[596..601] given)
          (NP (-NONE-:[601..601] *))
          (NP
            (NP (CD:[602..603] 5) (NN:[604..606] mg))
            (PP (SYM:[606..607] /)
              (NP (NN:[607..609] kg))))
          (ADVP (JJ:[610..614] oral)))))
    (,:[614..615] ,)
    (NP-SBJ-1
      (NP (DT:[616..617] a) (JJ:[618..622] mean) (NN:[623..627] tmax))
      (PP (IN:[628..630] of)
        (NP (CD:[631..634] 4.0) (NN:[635..637] hr))))
    (VP (VBD:[638..641] was)
      (VP (VBN:[642..650] observed)
        (NP-1 (-NONE-:[650..650] *))))
    (.:[650..651] .)))
;ERROR_Sentence has multiple Children (Sentence Error)[503..651]::S:S:

;sentence 7 Span:652..837
;Following iv  administration of the same respective doses, elimination t1/2
;in dogs and rats  averaged 1.2 and 4.5 hr. Absolute oral bioavailability of
;CI-966 was 100% in  both species.
;[723..727]:quantitative-name:"t1/2"
;[755..758]:quantitative-value:"1.2"
;[763..766]:quantitative-value:"4.5"
;[767..769]:quantitative-units:"hr"
;[804..810]:substance:"CI-966"
;[815..819]:quantitative-value:"100%"
(SENT
  (S
    (S-TMP
      (NP-SBJ (-NONE-:[652..652] *))
      (VP (VBG:[652..661] Following)
        (NP
          (NP (JJ:[662..664] iv) (NN:[666..680] administration))
          (PP (IN:[681..683] of)
            (NP (DT:[684..687] the) (JJ:[688..692] same)
                (JJ:[693..703] respective) (NNS:[704..709] doses))))))
    (,:[709..710] ,)
    (NP-SBJ
      (NP (NN:[711..722] elimination)
         (NN:[723..724] t) (CD:[724..725] 1) (SYM:[725..726] /)
         (CD:[726..727] 2))
      (PP-LOC (IN:[728..730] in)
        (NP (NNS:[731..735] dogs) (CC:[736..739] and) (NNS:[740..744] rats))))
    (VP (VBD:[746..754] averaged)
      (NP
        (NP (CD:[755..758] 1.2)
          (NML-1 (-NONE-:[758..758] *P*)))
        (CC:[759..762] and)
        (NP (CD:[763..766] 4.5)
          (NML-1 (NN:[767..769] hr)))))
    (.:[769..770] .))
  (S
    (NP-SBJ
      (NP (JJ:[771..779] Absolute) (JJ:[780..784] oral)
          (NN:[785..800] bioavailability))
      (PP (IN:[801..803] of)
        (NP (NN:[804..810] CI-966))))
    (VP (VBD:[811..814] was)
      (NP-PRD (CD:[815..818] 100) (NN:[818..819] %))
      (PP-LOC (IN:[820..822] in)
        (NP (DT:[824..828] both) (NNS:[829..836] species))))
    (.:[836..837] .)))
;ERROR_Sentence has multiple Children (Sentence Error)[652..837]::S:S:

;sentence 8 Span:838..975
;Following oral dosing of [14C]CI-966 HCl to dogs, fecal, and  urinary
;excretion accounted for 89% and 2.3% of the 14C dose, respectively.
;[863..878]:substance:"[14C]CI-966 HCl"
;[932..935]:quantitative-value:"89%"
;[940..944]:quantitative-value:"2.3%"
;[952..955]:substance:"14C"
(SENT
  (S
    (S-TMP
      (NP-SBJ (-NONE-:[838..838] *))
      (VP (VBG:[838..847] Following)
        (NP
          (NP (JJ:[848..852] oral) (NN:[853..859] dosing))
          (PP (IN:[860..862] of)
            (NP (NN:[863..874] -LSB-14C-RSB-CI-966) (NN:[875..878] HCl)))
          (PP (TO:[879..881] to)
            (NP (NNS:[882..886] dogs))))))
    (,:[886..887] ,)
    (NP-SBJ
      (NP (JJ:[888..893] fecal)
        (NML-1 (-NONE-:[893..893] *P*)))
      (,:[893..894] ,) (CC:[895..898] and)
      (NP (JJ:[900..907] urinary)
        (NML-1 (NN:[908..917] excretion))))
    (VP (VBD:[918..927] accounted)
      (PP-CLR (IN:[928..931] for)
        (NP
          (NP
            (NP (CD:[932..934] 89) (NN:[934..935] %))
            (CC:[936..939] and)
            (NP (CD:[940..943] 2.3) (NN:[943..944] %)))
          (PP (IN:[945..947] of)
            (NP (DT:[948..951] the) (NN:[952..955] 14C) (NN:[956..960] dose)))
          (,:[960..961] ,)))
      (ADVP (RB:[962..974] respectively)))
    (.:[974..975] .)))

;sentence 9 Span:976..1082
;In  bile-duct cannulated rats, biliary excretion is the major elimination
;pathway of  radioactivity (75%).
;[1077..1080]:quantitative-value:"75%"
(SENT
  (S
    (PP-LOC (IN:[976..978] In)
      (NP
        (ADJP
          (NML (NN:[980..984] bile) (HYPH:[984..985] -) (NN:[985..989] duct))
          (VBN:[990..1000] cannulated))
        (NNS:[1001..1005] rats)))
    (,:[1005..1006] ,)
    (NP-SBJ (JJ:[1007..1014] biliary) (NN:[1015..1024] excretion))
    (VP (VBZ:[1025..1027] is)
      (NP-PRD
        (NP (DT:[1028..1031] the) (JJ:[1032..1037] major)
            (NN:[1038..1049] elimination) (NN:[1050..1057] pathway))
        (PP (IN:[1058..1060] of)
          (NP (NN:[1062..1075] radioactivity))))
      (PRN (-LRB-:[1076..1077] -LRB-)
        (NP (CD:[1077..1079] 75) (NN:[1079..1080] %))
        (-RRB-:[1080..1081] -RRB-)))
    (.:[1081..1082] .)))

;sentence 10 Span:1083..1152
;Urinary and fecal excretion accounted for 4.1 and 12%,  respectively.
;[1125..1128]...[1135..1136]:quantitative-value:"4.1"..."%"
;[1133..1136]:quantitative-value:"12%"
(SENT
  (S
    (NP-SBJ
      (NP (JJ:[1083..1090] Urinary)
        (NML-2 (-NONE-:[1090..1090] *P*)))
      (CC:[1091..1094] and)
      (NP (JJ:[1095..1100] fecal)
        (NML-2 (NN:[1101..1110] excretion))))
    (VP (VBD:[1111..1120] accounted)
      (PP-CLR (IN:[1121..1124] for)
        (NP
          (NP (CD:[1125..1128] 4.1)
            (NML-1 (-NONE-:[1128..1128] *P*)))
          (CC:[1129..1132] and)
          (NP (CD:[1133..1135] 12)
            (NML-1 (NN:[1135..1136] %)))))
      (,:[1136..1137] ,)
      (ADVP (RB:[1139..1151] respectively)))
    (.:[1151..1152] .)))

;sentence 11 Span:1153..1271
;CI-966 does not induce or inhibit mouse hepatic mixed function  oxidases, as
;determined by hexobarbital sleeping time.
;[1153..1159]:substance:"CI-966"
;[1217..1225]:substance:"oxidases"
;[1244..1256]:substance:"hexobarbital"
(SENT
  (S
    (NP-SBJ (NN:[1153..1159] CI-966))
    (VP (VBZ:[1160..1164] does) (RB:[1165..1168] not)
      (VP (VB:[1169..1175] induce) (CC:[1176..1178] or)
          (VB:[1179..1186] inhibit)
        (NP (NN:[1187..1192] mouse) (JJ:[1193..1200] hepatic)
          (NML (VBN:[1201..1206] mixed) (NN:[1207..1215] function))
          (NNS:[1217..1225] oxidases))
        (,:[1225..1226] ,)
        (SBAR-ADV (IN:[1227..1229] as)
          (S
            (NP-SBJ-1 (-NONE-:[1229..1229] *))
            (VP (VBN:[1230..1240] determined)
              (NP-1 (-NONE-:[1240..1240] *))
              (PP (IN:[1241..1243] by)
                (NP-LGS (NN:[1244..1256] hexobarbital)
                        (NN:[1257..1265] sleeping) (NN:[1266..1270] time))))))))
    (.:[1270..1271] .)))

;section 12 Span:1275..1319
;PMID: 8272405 [PubMed - indexed for MEDLINE]
(SEC
  (FRAG (NNP:[1275..1279] PMID) (::[1279..1280] :) (CD:[1281..1288] 8272405)
        (NN:[1289..1290] -LSB-) (NNP:[1290..1296] PubMed) (::[1297..1298] -)
        (NN:[1299..1306] indexed) (IN:[1307..1310] for)
        (NNP:[1311..1319] MEDLINE-RSB-)))