Neuroleptička svojstva urapidila u uvjetima in vitro i in vivo

doctoral thesis

• Title (english): Neuroleptic properties of urapidil in condition in vitro and in vivo
• Author: Božo Radić
• Mentor: Predrag Sikirić (mentor); MBZ: 117454
• Mentor: Maja Jazvinšćak Jembrek (sumentor); MBZ: 233712
• Committee member: xxx xxx (predsjednik povjerenstva); MBZ: xxx
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2016, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

Istražena su neuroleptička svojstva urapidila u štakora u uvjetima in vitro i in vivo. Urapidil je antihipertenziv, agonist centralnih 5-HT1a receptora i antagonist perifernih alfa 1 receptora s utjecajem na dopaminergičku transmisiju. Na stanicama PC12 i SH-SY5Y urapidil u dozi od 100 i 200 µM ne djeluje antioksidacijski (za razliku od kvercetina), niti zaustavlja smrt stanica izazvanu metamfetaminom (kao i haloperidol), ali dovodi do zaustavljanja aktivnosti efektorskih kaspaza 3/7 mitohondrijskog puta. In vivo u dozi od 0.25, 0.5 i 1 mg/štakoru intraperitonealno (i.p.), urapidil dovodi do povećanja lokomocije, bez izazivanja abnormalnih kretnji ili stereotipija karakterističnih za metamfetamin. Doze od 15, 20 i 25 mg/štakoru i.p. dovode do progresivne katalepsije, dok doza od 25 mg/štakoru i.p. urapidila u predtretmanu i posttretmanu zaustavlja hiperlokomociju i stereotipije izazvane metamfetaminom. Urapidil blokira aktivnost kaspaza 3/7 nakon primjene metamfetamina i iskazuje jasna neuroleptička svojstva, vjerojatno vežući se za dopaminske (D2) receptore.

Abstract (english)

Neuroleptic properties of urapidil were investigated in vitro and in vivo models in rats. Urapidil is an antihypertensive agent, agonist of central 5-HT1a and antagonist of peripheral alpha 1 receptors, with the effect on dopaminergic transmission. On PC12 and SH-SY5Y cells urapidil at doses of 100 and 200 µM is not acting like antioxidant (like quercetin does), nor stops cell death (like haloperidol) caused by methamphetamine, but blocks the activity of effector caspase 3/7 mitochondrial pathway. In vivo at a dose of 0.25, 0.5 and 1 mg/rat intraperitoneally (i.p.) it increases locomotion, but without causing abnormal movement or stereotypy like metamphetamine does. At doses of 15, 20 and 25 mg/rat i.p. urapidil causes progressive catalepsy. When applied as pretreatment and posttreatment it antagonizes metamphetamine induced hyperlocomotion and stereotypy. Urapidil blocks the activity of caspase 3/7 following administration of methamphetamine and expresses clear neuroleptic properties likely by binding to dopamine (D2) receptors.

• Keywords: urapidil; neuroleptici; metamfetamin; stanice PH12; stanice SYHS5; štakori
• Keywords (english): urapidil; neuroleptics; metamphetamine; cells PH12; cells SYHS5; rats
• Language: croatian
• URN:NBN: urn:nbn:hr:217:036239
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-16 10:21:26