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master's thesis
Farmakokinetika i farmakodinamika učinkovitog reaktivatora acetilkolinesteraze
Zagreb: University of Zagreb, Faculty of Science, 2021. urn:nbn:hr:217:129908
Pavošević, Kristian
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Pavošević, K. (2021). Farmakokinetika i farmakodinamika učinkovitog reaktivatora acetilkolinesteraze (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:129908

Pavošević, Kristian. "Farmakokinetika i farmakodinamika učinkovitog reaktivatora acetilkolinesteraze." Master's thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:129908

Pavošević, Kristian. "Farmakokinetika i farmakodinamika učinkovitog reaktivatora acetilkolinesteraze." Master's thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:129908

Pavošević, K. (2021). 'Farmakokinetika i farmakodinamika učinkovitog reaktivatora acetilkolinesteraze', Master's thesis, University of Zagreb, Faculty of Science, accessed 22 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:129908

Pavošević K. Farmakokinetika i farmakodinamika učinkovitog reaktivatora acetilkolinesteraze [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2021 [cited 2024 November 22] Available at: https://urn.nsk.hr/urn:nbn:hr:217:129908

K. Pavošević, "Farmakokinetika i farmakodinamika učinkovitog reaktivatora acetilkolinesteraze", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:217:129908

Metadata
TitleFarmakokinetika i farmakodinamika učinkovitog reaktivatora acetilkolinesteraze
Title (english)Pharmacokinetics and pharmacodynamics of an efficient acetylcholinesterase reactivator
AuthorKristian Pavošević
MentorZrinka Kovarik (mentor)
MentorNada Oršolić (sumentor)
Committee memberNada Oršolić (predsjednik povjerenstva)
Committee memberSven Jelaska (član povjerenstva)
Committee memberMartina Šeruga Musić (član povjerenstva)
Committee memberPetar Kružić (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2021-01-27, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
Acetilkolinesteraza (AChE; E.C. 3.1.1.7) je enzim intenzivno istraživan u području biokemije i toksikologije zbog svoje iznimne važnosti u homeostazi organizma. Fiziološki supstrat AChE je acetilkolin (ACh), živčani prijenosnik u središnjem (SŽS) i perifernom (PŽS) živčanom sustavu. Izloženost organofosfornim (OP) spojevima uzrokuje akutnu toksičnost koja je rezultat inhibicije aktivnosti AChE uslijed čega je zaustavljena kataliza hidrolize i razgrađivanje ACh prilikom čega dolazi do poremećaja prijenosa živčanih impulsa unutar kolinergičnih sinapsi SŽS-a i PŽS-a. Kao terapija uslijed trovanja OP spojevima koriste se oksimski reaktivatori inhibirane AChE (pr. 2-PAM, HI-6, obidoksim, TMB-4), ali njihova je učinkovitost ograničena zbog visoke specifičnosti konjugata kojeg stvaraju enzim i OP spoj te zbog slabog prolaska i djelovanja u mozgu. Cilj ovog diplomskog rada bio je utvrditi farmakološke karakteristike novosintetiziranog hidroksipiridinskog reaktivatora AChE, JR595, dizajniranog za prolazak u SŽS. In silico metode korištene su za predikciju parametara koji opisuju farmakokinetički profil oksima, a in vitro kinetičke metode za određivanje njegove farmakodinamike na modelu mišje i ljudske AChE pri sobnoj i fiziološkoj temperaturi. Konačno, dobiveni rezultati uspoređeni su s objavljenim in vivo učincima JR595 oksima kao antidota za trovanje OP spojevima kako bi se utvrdile strukturne i farmakološke prednosti ili nedostatci ispitivanog reaktivatora.
Abstract (english)
Acetylcholinesterase (AChE; E.C. 3.1.1.7) is an intensively investigated enzyme in fields of biochemistry and toxicology. Acetylcholine (ACh), a substrate molecule for AChE, acts as a neurotransmitter in central (CNS) and peripheral (PNS) nervous system. Exposure to organophosphorus (OP) compounds induces an acute toxicity due to AChE inhibition that stops the catalysis of ACh hydrolysis and degradation and impairs nerve signal transduction in cholinergic synapses of CNS and PNS. Available therapy for OP intoxication includes oxime antidotes with potential to reactivate inhibited AChE (e.g., 2-PAM, HI-6, obidoxime), but their efficiency is limited due to the high specificity of enzyme-OP conjugate and poor penetration and effect in the brain. The aim of this thesis was to evaluate pharmacological characteristics of the newly-synthesized hydroxypyridine AChE reactivator, JR595, designed to pass through the BBB (engl. blood-brain barrier) and affect the CNS. Used methods include in silico predictions of the parameters that describe pharmacokinetic profile of the oxime and in vitro kinetic methods for description of pharmacodynamics on human and mouse AChE model at room and physiological temperature. Finally, obtained results were compared to published in vivo effects of JR595 for OP intoxication in order to determine structural and pharmacological advantages or disadvantages of JR595.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:129908
Study programmeTitle: Experimental Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2021-02-12 14:06:37