Fenibuta racemāta un tā enantiomēru farmakoloģiskā aktivitāte un darbības mehānismi
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Latvijas Universitāte
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Abstract
Darbā tika pētīta fenibuta (3-fenil-4-aminosviestskābe) un tā enantiomēru farmakoloģiskā darbība un darbības mehānismi dzīvnieku uzvedības testos un radioligandu saistīšanās eksperimentos. Ir zināms, ka fenibuts ir nootropa zāļu viela, kas ietekmē GABA-erģisko sistēmu un klīniskajā praksē to lieto racemāta formā.
Bakalaura darba ietvaros uzvedības testos mēs novērojām, ka R-fenibuts bija 2-3 reizes aktīvāks par fenibuta racemātu, savukārt S-fenibuts bija neaktīvs, tajā pašā laikā toksicitāte R-fenibutam bija līdzvērtīga fenibuta racemāta toksicitātei. Radioligandu saistīšanās eksperimentos R-fenibuta saistīšanās ar GABAB receptoriem bija divas reizes izteiktāka nekā fenibuta racemātam, turpretim S-fenibuts nesaistījās pie šī receptora. Savienojumu darbības mehānismu noskaidrošanai izmantojām GABAB receptoru selektīvo antagonistu, kas pilnībā bloķēja R-fenibuta antidepresīvo, pretsāpju un nomierinošu darbību.
No iegūtajiem rezultātiem mēs varam secināt, ka fenibuta racemāta farmakaloģiskā aktivitāte ir balstīta uz R-fenibuta darbību un tā saistīšanos ar GABAB receptoriem.
The aim of this study was to research the effects and the pharmacological activity of racemic phenibut (3-phenil-4-aminobutyric acid) and its optical enantiomers in pharmacological tests and the radioligand binding experiments. It is known that phenibut is a GABA-mimetic psychotropic drug which is clinically used in its racemic form. In the pharmacological tests we observed that R-phenibut turned out to be two to three times more potent than racemic phenibut, although the toxicity for the two was similar. In contrast, S-phenibut was inactive. The radioligand binding experiments with GABAB receptors revealed that affinity constants for R-phenibut were twice as high as the one with racemic phenibut, though S-phenibut didn’t show any affinity. To find out the activity of the compounds we used selective GABAB receptor antagonist that inhibited the antidepressant, sedative and analgesic effects of R-pfenibut. We conclude that the pharmacological activity of racemic phenibut relies on R-phenibut and this correlates to the binding affinity of enantiomers of phenibut to the GABAB receptors.
The aim of this study was to research the effects and the pharmacological activity of racemic phenibut (3-phenil-4-aminobutyric acid) and its optical enantiomers in pharmacological tests and the radioligand binding experiments. It is known that phenibut is a GABA-mimetic psychotropic drug which is clinically used in its racemic form. In the pharmacological tests we observed that R-phenibut turned out to be two to three times more potent than racemic phenibut, although the toxicity for the two was similar. In contrast, S-phenibut was inactive. The radioligand binding experiments with GABAB receptors revealed that affinity constants for R-phenibut were twice as high as the one with racemic phenibut, though S-phenibut didn’t show any affinity. To find out the activity of the compounds we used selective GABAB receptor antagonist that inhibited the antidepressant, sedative and analgesic effects of R-pfenibut. We conclude that the pharmacological activity of racemic phenibut relies on R-phenibut and this correlates to the binding affinity of enantiomers of phenibut to the GABAB receptors.