Receptors, GABA-B

Publication Title: 
Bioorganic & Medicinal Chemistry Letters

Two new GABA derivatives, 1 and 2, were synthesized and tested for their capacity to display CNS activity, which was assessed by determining the effects on the duration of pentobarbital-induced hypnosis in rats. Compound 1, peripherally injected, significantly prolonged the hypnosis time, a typical GABA-mimetic effect, while both intracerebroventricular and intravenous administration of compound 2 surprisingly shortened the hypnotic effect in an atropine-sensitive way. The study was extended also to compounds 1a, 1b and 2a, putative oxidative/hydrolytic metabolites of 1 and 2.

Carelli, Vincenzo
Liberatore, Felice
Scipione, Luigi
Giorgioni, Gianfabio
Di Stefano, Antonio
Impicciatore, Mariannina
Ballabeni, Vigilio
Calcina, Francesco
Magnanini, Francesca
Barocelli, Elisabetta
Publication Title: 
Journal of Pharmacological Sciences

The endogenous brain constituent, gamma-hydroxybutyric acid (GHB), as well as its prodrug, gamma-butyrolactone (GBL), have recently gained interest in the drug addiction field due to their abuse potential and fatalities caused by overdose. It is known that GHB has two sites of actions: the gamma-aminobutyric acid(B) (GABA(B)) receptor and a specific-GHB binding site. The present study was designed to extend to GBL the investigations on the contribution of the GABA(B) receptor and the specific-GHB binding site to its in vivo effects.

Carai, Mauro A. M.
Lobina, Carla
Maccioni, Paola
Cabras, Claudia
Colombo, Giancarlo
Gessa, Gian Luigi
Publication Title: 
Journal of Medicinal Chemistry

Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino)thiophene derivatives. Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABAB receptor by potentiating GTP?S stimulation induced by GABA at 2.5 and 25 ?M while failing to exhibit intrinsic agonist activity. Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically.

Mugnaini, Claudia
Pedani, Valentina
Casu, Angelo
Lobina, Carla
Casti, Alberto
Maccioni, Paola
Porcu, Alessandra
Giunta, Daniela
Lamponi, Stefania
Solinas, Maurizio
Dragoni, Stefania
Valoti, Massimo
Colombo, Giancarlo
Castelli, Maria Paola
Gessa, Gian Luigi
Corelli, Federico
Publication Title: 
Acta Pharmacologica Sinica

AIM: Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) provides neuroprotection against apoptosis in a transient middle cerebral artery occlusion (MCAo) model. This study was to further investigate the anti-apoptotic effect of FA during reperfusion after cerebral ischemia. METHODS: Rats were subjected to 90 min of cerebral ischemia followed by 3 or 24 h of reperfusion after which they were sacrificed.

Cheng, Chin-Yi
Su, Shan-yu
Tang, Nou-Ying
Ho, Tin-Yun
Lo, Wan-yu
Hsieh, Ching-Liang
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