• Something wrong with this record ?

Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning

K. Tekes, G. Karvaly, S. Nurulain, K. Kuca, K. Musilek, E. Adeghate, YS. Jung, H. Kalász,

. 2019 ; 310 (-) : 108737. [pub] 20190704

Language English Country Ireland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc19034461

AIMS: K117 and K127 are bis-pyridinium aldoximes but K117 is a bis-pyridinium bis-aldoxime while K127 has only one single aldoxime in addition to its amide substituent. Is there any difference in pharmacokinetics in these compounds that otherwise have the same chemical structure? Both K117 and K127 are developed as antidotes in acetylcholinesterase and butyrylcholinesterase poisoning in terrorist attacks or intoxication with other organophosphorous compounds. Their distributions have been scouted in the bodies of rats. MAIN METHODS: White male Wistar rats were intramuscularly injected. The animals were sacrificed, tissue samples were homogenized, and either K117 or K127 concentrations were determined using reversed-phase high-performance liquid chromatography. KEY FINDINGS: Both K117 and K127 were present in all tissues that were analyzed including blood (serum), the brains, cerebrospinal fluid, the eyes, livers, kidneys, lungs and testes. Their pharmacokinetics and body distributions are similar. SIGNIFICANCE: Either K117 or K127 meets the essential requirements for antidotes. Dose dependence and kinetics of their distribution were compared to that of other pyridinium aldoximes.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19034461
003      
CZ-PrNML
005      
20191008124849.0
007      
ta
008      
191007s2019 ie f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.cbi.2019.108737 $2 doi
035    __
$a (PubMed)31279792
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ie
100    1_
$a Tekes, K $u Department of Pharmacodynamics, Semmelweis University, H-1089, Budapest, Nagyvárad tér 4, Hungary. Electronic address: drtekes@gmail.com.
245    10
$a Pharmacokinetics of K117 and K127, two novel antidote candidates to treat Tabun poisoning / $c K. Tekes, G. Karvaly, S. Nurulain, K. Kuca, K. Musilek, E. Adeghate, YS. Jung, H. Kalász,
520    9_
$a AIMS: K117 and K127 are bis-pyridinium aldoximes but K117 is a bis-pyridinium bis-aldoxime while K127 has only one single aldoxime in addition to its amide substituent. Is there any difference in pharmacokinetics in these compounds that otherwise have the same chemical structure? Both K117 and K127 are developed as antidotes in acetylcholinesterase and butyrylcholinesterase poisoning in terrorist attacks or intoxication with other organophosphorous compounds. Their distributions have been scouted in the bodies of rats. MAIN METHODS: White male Wistar rats were intramuscularly injected. The animals were sacrificed, tissue samples were homogenized, and either K117 or K127 concentrations were determined using reversed-phase high-performance liquid chromatography. KEY FINDINGS: Both K117 and K127 were present in all tissues that were analyzed including blood (serum), the brains, cerebrospinal fluid, the eyes, livers, kidneys, lungs and testes. Their pharmacokinetics and body distributions are similar. SIGNIFICANCE: Either K117 or K127 meets the essential requirements for antidotes. Dose dependence and kinetics of their distribution were compared to that of other pyridinium aldoximes.
650    _2
$a acetylcholinesterasa $x chemie $7 D000110
650    _2
$a zvířata $7 D000818
650    _2
$a antidota $x farmakokinetika $7 D000931
650    _2
$a butyrylcholinesterasa $x chemie $7 D002091
650    _2
$a chemické bojové látky $x farmakokinetika $7 D002619
650    _2
$a cholinesterasové inhibitory $x farmakokinetika $7 D002800
650    _2
$a reaktivátory cholinesterázy $x farmakokinetika $7 D002801
650    _2
$a organofosfáty $x antagonisté a inhibitory $7 D010755
650    _2
$a oximy $x analýza $x farmakokinetika $7 D010091
650    _2
$a pyridinové sloučeniny $x analýza $x farmakokinetika $7 D011726
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a potkani Wistar $7 D017208
650    _2
$a tkáňová distribuce $7 D014018
655    _2
$a časopisecké články $7 D016428
700    1_
$a Karvaly, G $u Department of Laboratory Medicine, Semmelweis University, H-1089, Budapest, Nagyvárad tér 4, Hungary. Electronic address: karvaly.gellert_balazs@med.semmelweis-univ.hu.
700    1_
$a Nurulain, S $u Comsats, Islamabad, Pakistan. Electronic address: syed.nurulain@comsats.edu.pk.
700    1_
$a Kuca, K $u Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic.
700    1_
$a Musilek, K $u Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic. Electronic address: kamil.musilek@uhk.cz.
700    1_
$a Adeghate, E $u Department of Anatomy, United Arab Emirates University, Al Ain, United Arab Emirates. Electronic address: eadeghate@uaeu.ac.ae.
700    1_
$a Jung, Y-S $u Medicinal Science Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea. Electronic address: ysjung@krict.re.kr.
700    1_
$a Kalász, H $u Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089, Budapest, Nagyvárad tér 4, Hungary. Electronic address: drkalasz@gmail.com.
773    0_
$w MED00002111 $t Chemico-biological interactions $x 1872-7786 $g Roč. 310, č. - (2019), s. 108737
856    41
$u https://pubmed.ncbi.nlm.nih.gov/31279792 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20191007 $b ABA008
991    __
$a 20191008125305 $b ABA008
999    __
$a ok $b bmc $g 1451121 $s 1073011
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 310 $c - $d 108737 $e 20190704 $i 1872-7786 $m Chemico-biological interactions $n Chem Biol Interact $x MED00002111
LZP    __
$a Pubmed-20191007

Find record

Citation metrics

Archiving options