F-phenibut (β-(4-Fluorophenyl)-GABA), a potent GABAB receptor agonist, activates an outward-rectifying K+ current and suppresses the generation of action potentials in mouse cerebellar Purkinje cells
Autor: | Tomohiko Irie, Ruri Kikura-Hanajiri, Daiju Yamazaki |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Pharmacology Agonist Chemistry GABAA receptor medicine.drug_class Phenibut GABAB receptor In vitro Nootropic 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Baclofen nervous system medicine Extracellular 030217 neurology & neurosurgery medicine.drug |
Zdroj: | European Journal of Pharmacology. 884:173437 |
ISSN: | 0014-2999 |
Popis: | The GABA analog phenibut (β-Phenyl-GABA) is a GABAB receptor agonist that has been licensed for various uses in Russia. Phenibut is also available as a dietary supplement from online vendors worldwide, and previous studies have indicated that phenibut overdose results in intoxication, withdrawal symptoms, and addiction. F-phenibut (β-(4-Fluorophenyl)-GABA), a derivative of phenibut, has not been approved for clinical use. However, it is also available as a nootropic supplement from online suppliers. F-phenibut binds to GABAB with a higher affinity than phenibut; therefore, F-phenibut may lead to more serious intoxication than phenibut. However, the mechanisms by which F-phenibut acts on GABAB receptors and influences neuronal function remain unknown. In the present study, we compared the potency of F-phenibut, phenibut, and the GABAB agonist (±)-baclofen (baclofen) using in vitro patch-clamp recordings obtained from mouse cerebellar Purkinje cells slice preparations Our findings indicate that F-phenibut acted as a potent GABAB agonist. EC50 of outward current density evoked by the three GABAB agonists decreased in the following order: phenibut (1362 μM) > F-phenibut (23.3 μM) > baclofen (6.0 μM). The outward current induced by GABAB agonists was an outward-rectifying K+ current, in contrast to the previous finding that GABAB agonists activates an inward-rectifying K+ current. The K+ current recorded in the present study was insensitive to extracellular Ba2+, intra- or extracellular Cs+, and intra- or extracellular tetraethylammonium-Cl. Moreover, F-phenibut suppressed action potential generation in Purkinje cells. Thus, abuse of F-phenibut may lead to severe damage by inhibiting the excitability of GABAB-expressing neurons. |
Databáze: | OpenAIRE |
Externí odkaz: |