GABA sustav u zdravlju i bolesti

master's thesis

• Title (english): The GABA system in health and sickness
• Author: Rafaela Bilić
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Živka Juričić (član povjerenstva)
• Committee member: Maja Ortner Hadžiabdić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2019-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

GABA, glavni inhibicijski neurotransmitor u središnjem živčanom sustavu, ima ključnu ulogu u osiguravanju normalne moždane funkcije. Stoga će bilo kakva promjena u GABA-ergičkoj transmisiji rezultirati nastankom različitih psihijatrijskih i neuroloških oboljenja.
Cilj ovog diplomskog rada bio je opisati najvažnije lijekove s djelovanjem na različite sastavnice GABA-ergične sinapse.
Budući da GABA ispoljava glavninu učinka preko GABAA-receptora, klinički su najznačajniji upravo oni lijekovi koji svoje terapijsko djelovanje ostvaruju moduliranjem tih receptora. Najpoznatiji od njih su benzodiazepini, barbiturati i Z-lijekovi koji se koriste u širokom području indikacija počevši od anksioznih poremećaja i nesanice pa sve do mišićnih spazama i epilepsije.
Usprkos velikom broju istraživanja u posljednih 50-ak godina, još uvijek ne jenjava interes za istraživanjem GABA sustava u zdravlju i bolesti. Ta istraživanja su rezultirala razvojem novih molekula indiciranih u stanjima za koja donedavno nije postojala adekvatna terapija kao što je slučaj breksanolona koji je 2019. registriran kao prvi lijek za olakšavanje simptoma postporođajne depresije.
Otkriće anksiolitičkog učinka kurkumola iz podanka kurkume pobudio je interes za ispitivanjem i drugih molekula iz prirodnih izvora koji bi postigli bolji ili podjednak terapijski učinak kod najčešće primjenjivanih GABA modulatora benzodiazepina, ali uz značajno smanjenje nuspojava, pogotovo onih povezanih s njihovom dugotrajnom primjenom.

Abstract (english)

GABA, the major inhibitory neurotransmitter in the central nervous system, plays a key role in maintaining normal brain function. Therefore, any alteration in GABAergic transmission will result in the development of numerous psychiatric and neurological disorders.
The aim of this master's thesis was to describe the role of the most important medications that act on different elements of GABA synapse.
Given the fact that GABA exerts its effects via GABAA receptors, many clinically important drugs are thouse that achieve their specific therapeutic action by targeting GABAA receptor complex. Of particular importance are benzodiazepines, barbiturates and Z-drugs which are used for numerous indications, including anxiety, insomnia, muscle relaxation and epilepsy.
Despite numerous studies conducted over the last fifty years ago, there is still a growing interest in exploring GABA system in health and disease with the aim of fully unlocking its therapeutic potential. Some of these experiments had resulted in the discovery of molecules which proved to be valuable for novel indications such as brexanolone which received its approval in 2019., becoming the first drug to be specifically approved for postpartum depression.
The discovery of anxyiolytic potential of curcumol for the rhizome of Curcuma loga L. (Zingiberaceae) had resulted in an increased number of testing other natural compounds that will be as therapeutically active as benzodiazepines, the most widely udes class of GABA modulators, but without undesirable side effects, especially those associated with their long-term administration.

• Keywords: GABA; GABA receptori; farmakologija; depolarizacija; anksiolitici; benzodijazepini; barbiturati; Z-lijekovi; toksikologija; antikonvulzivi; breksanolon
• Keywords (english): GABA; GABA receptors; pharmacology; depolarization; anxiolytics; benzodiazepines; barbiturates; Z-drugs; toxicity; anticonvulsants; brexanolone
• Language: croatian
• URN:NBN: urn:nbn:hr:163:642734
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-22 12:40:43