Farmakološka modulacija glutamatergičke transmisije u liječenju bolesti središnjeg živčanog sustava

master's thesis

• Title (english): Pharmacological modulation of glutamatergic transmission in the treatment of central nervous system diseases
• Author: Lucija Nemarnik
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Kristina Pavić (član povjerenstva)
• Committee member: Sandra Šupraha-Goreta (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2025-02-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Glutamat je glavni ekscitatorni neurotransmiter u mozgu i kao takav je ključan za ekscitatornu
transmisiju. Poremećaj glutamatergičke transmisije može dovesti do razvoja širokog spektra bolesti
središnjeg živčanog sustava te ubrzati njihovu progresiju. Najčešća posljedica povećane
glutamatergičke transmisije je razvoj ekscitotoksičnosti uslijed pretjeranog otpuštanja glutamata i
aktivacije glutamatnih receptora. Modulacija ove transmisije može imati pozitivan učinak u terapiji niza
bolesti, kao što su epilepsija, shizofrenija, Alzheimerova bolest i mnoge druge.
Ovaj diplomski rad daje sistematski pregled terapijskih mogućnosti usmjerenih na modulaciju
glutamatergičke transmisije. Prikazane su pozitivne i negativne strane te farmakološke karakteristike
dostupnih lijekova. Zatim su prikazani lijekovi u prekliničkim i kliničkim fazama razvoja te oni čiji je
razvoj zaustavljen, ali koji pružaju kvalitetan temelj za razvoj novih lijekova. Rad se dotiče i drugih
mogućnosti farmakološke i ne-farmakološke modulacije glutamatergičke transmisije, poput genske
terapije. Temeljem velikog interesa za istraživanja neurobiologije i uključenosti glutamatergičke
transmisije u patofiziološke procese, kao i intenzivnog razvoja lijekova s modulatornim djelovanjem na
glutamatergički sustav, za očekivati je da će u budućnosti farmakološka modulacija ovog sustava biti
temelj liječenja širokog spektra bolesti SŽS-a.

Abstract (english)

Glutamate is the primary excitatory neurotransmitter in the brain, playing a crucial role in excitatory transmission.
Disruptions in glutamatergic transmission can lead to the development of a wide range of central nervous system
disorders and accelerate their progression. The most common disturbance in glutamatergic transmission is the
development of excitotoxicity, which results from excessive glutamate release and activation of glutamate receptors.
Modulation of this transmission may have a beneficial effect in the treatment of various diseases, such as epilepsy,
schizophrenia, Alzheimer's disease and many others.
This review thesis provides a systematic overview of therapies focused on the modulation of glutamatergic
transmission. It presents both positive and negative aspects, as well as pharmacological characteristics of current
therapies. Additionally, drugs in preclinical and clinical development phases, as well as those whose development has
been discontinued but serve as a solid foundation for new drug development, are discussed. The thesis also examines
other pharmacological and non-pharmacological options for modulation of glutamatergic transmission, such as gene
therapy. Based on the significant interest in neurobiology research and the involvement of glutamategic transmission
in pathophysiology processes, as well as the intensive development of drugs with modulatory effects on glutamatergic
system, it is to be expected that in the future, pharmacological modulation of this system will form the foundation for
the treatment of a wide range of central nervous system diseases.

• Keywords: glutamat; glutamatergička transmisija; glutamatni receptori; antagonisti glutamatnih receptora; modulatori glutamata; ekscitotoksičnost; redukcija ekscitacije; lijekovi u razvoju; genska terapija
• Keywords (english): glutamate; glutamatergic transmission; glutamate receptors; glutamate receptors antagonists; glutamate modulators; excitotoxicity; reducing excitation; drug sin research; gene therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:163:593961
• Study programme: Title: Pharmacy - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar farmacije (sveučilišni magistar farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-04-02 12:17:25