Med.Inter.Rev. 2014, 102, 32-40.

Pharmacological activity of novel GABA re-uptake inhibitors in mice


PODKOWA Adrian1., GRZYWA Anna1., LECHOCKA Anna1.,SZLONZAK Agata1., KOWALCZYK Paula2.,KULIG Katarzyna2., FILIPEK Barbara1.SAŁAT Kinga11.

1.Katedra Farmakodynamiki, Wydział Farmaceutyczny, Uniwersytet Jagielloński, Collegium Medicum, ul. Medyczna 9, 30-688 Kraków, Polska
2.Zakład Fizykochemicznej Analizy Leku, Katedra Chemii Farmaceutycznej, Wydział Farmaceutyczny, Uniwersytet Jagielloński, Collegium Medicum, ul. Medyczna 9, 30-688 Kraków, Polska


Abstract
Γ-aminobutyric acid (GABA) is a widely distributed neurotransmitter in the mammalian central nerv-ous system. The GABAergic neurotransmission is involved in numerous processes, including neuronal excitability and mood disorders. GABA is removed from the synaptic cleft by specific proteins called plasma membrane GABA transporters. In the present work we focus on antinociceptive and antidepres-sant-like properties of four new GABA re-uptake inhibitors. These compounds are N-benzylamide derivatives ofGABA. We alsoinvestigate their impact on animal’ locomotor activity and motor coordina-tion. All the examined compounds present analgesic activity in the hot plate test. Most of them alsodemonstrateantidepressant-like properties in the forced swim test in mice. Similarly to tiagabine, the test compounds significantly affect locomotor activity and some of them cause motor coordination impairments. The obtained results suggest that compounds targeting at GABA transporters may exert analgesic and antidepressant-like properties.
Keywords:γ-aminobutyric acid, γ-hydroxybutyric acid, GABA transporters, tiagabine, pain, depression


Oryginal language: Polish

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