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abstract@kcsnet.or.kr
결제문의
member@kcsnet.or.kr
현재 가능한 작업은 아래와 같습니다.
09월 06일 15시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능
제112회 대한화학회 학술발표회, 총회 및 기기전시회 안내
NON-REACTIVATING PROPERTIES OF OXIME REACTIVATORS
등록일
2013년 9월 5일 16시 29분 57초
접수번호
1431
발표코드
MEDI.P-959
이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
10월 16일 (수요일) 16:00~19:00
발표형식
포스터
발표분야
의약화학
저자 및
공동저자
O. Soukup
*
, D. Jun
, Gunnar Tobin
1
, K. Kuca
University hospital of Hradec Kralove, Czech Republic, Czech Republic
1
Department of Pharmacology, Sahlgrenska Academy, University of Gothenburg, Sweden, Czech Republic
※ 국외소속으로 등록된 저자의 승인여부는 최소 3일이내 발표자 email로 알려드립니다.
승인 4건
Current treatment of organophosphorus (OP) poisoning, originating as irreversible inhibition of acetylcholinesterase (AChE) and resulting as the overstimulation and of cholinergic receptors by acetylcholine (ACh), consists of the administration of atropine and oxime reactivators. The reactivators´ mechanism of action seems to be simple: restore the activity of OP-inhibited AChE. However, rather complex mechanism has been ascribed to oxime reactivators. They act at several levels of the cholinergic transmission including synthesis, release, inactivation and re-uptake of the transmitter, especially the interaction with muscarinic and nicotinic receptors may be of therapeutic benefit in the treatment of OP poisoning. Our study focuses on this non-reactivation properties of oximes, especially on the interaction with postsynaptic muscarinic and nicotinic receptors. Furthermore, the effect on AChE and re-uptake transport system (HACU) has been investigated as well. Both in vitro receptor binding studies, isolated organ´s contraction studies, patch-clamp etc and in vivo techniques were used. The results confirmed that oxime reactivators are also inhibitors of AChE (IC50 in micromolar range) and may influence the release of ACh via the interaction with re-uptake transport system (HACU) a key-regulatory system, which delivers choline for the synthesis de novo. In-vitro and in-vivo experiments comprehensively proved inhibitory effects of studied oximes on nicotinic receptors. Although, the IC50 values were in the hundreds of micromoles, even a weak inhibition may speak in favor of the treatment with reactivators. Especially when atropine does not affect nicotinic receptors at all and nicotinic symptoms are usually responsible for the death of a victim. Muscarinic antagonism has also been descibed by both in-vitro and in-vivo experiments as well. Although, the mechanism of binding has not been satisfactorily explained a weak inhibition was observed (atropine had at least 3-fold higher efficacy). However, even a weak inhibition may play an important role in the treatment of OP poisoning, in particular, in the case of “aging”. We can conclude that oxime reactivators´ mechanism of action represents much more complex system than only reactivation. This work was supported by the grant of Ministry of Health (Czech Republic) No. NT12062 and A long ― term organization development plan 1011
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