Phenotypical Screening on Neuronal Plasticity in Hippocampal-Prefrontal Cortex Connectivity Reveals an Antipsychotic with a Novel Profile.

Dysfunction in the hippocampus-prefrontal cortex (H-PFC) circuit is a critical determinant of schizophrenia. Screening of pyridazinone-risperidone hybrids on this circuit revealed EGIS 11150 (S 36549). EGIS 11150 induced theta rhythm in hippocampal slice preparations in the stratum lacunosum molecular area of CA1, which was resistant to atropine and prazosin.

S29434, a Quinone Reductase 2 Inhibitor: Main Biochemical and Cellular Characterization.

Quinone reductase 2 (QR2, E.C. 1.

Persistent therapeutic effect of a novel α5-GABA receptor antagonist in rodent preclinical models of vascular cognitive impairment.

This study examined the potential of the selective extra-synaptic α5-GABA receptor inhibitor S44819 (Egis-13529) to improve cognitive performance in preclinical models of vascular cognitive impairment (VCI). Chronic hypoperfusion of the brain in mice was induced by permanent occlusion of the right common carotid artery (rUCO). rUCO induced impairments of cognitive function in the object recognition test (OR) and the rewarded T-maze (RTM).

Loop F of the GABA receptor alpha subunit governs GABA potency.

Gamma-amino butyric acid (GABA) is an abundant neurotransmitter in the CNS. GABAergic interneurons orchestrate pyramidal neurons in the cerebral cortex, and thus control learning and memory. Ionotropic receptors for GABA (GABAR) are heteropentameric complexes of α, β and γ integral membrane-protein subunits forming Cl -channels operated by GABA, which are vital for brain function and are important drug targets.

Selective inhibition of extra-synaptic α5-GABA receptors by S44819, a new therapeutic agent.

In the mammalian central nervous system (CNS) GABA receptors (GABARs) mediate neuronal inhibition and are important therapeutic targets. GABARs are composed of 5 subunits, drawn from 19 proteins, underpinning expression of 20-30 GABAR subtypes. In the CNS these isoforms are heterogeneously expressed and exhibit distinct physiological and pharmacological properties.