GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy.
Bottom Line: Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations.Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions.GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE.
Affiliation: Umecrine Cognition AB, Solna, Sweden; Umeå Neurosteroid Research Center, Department of Clinical Sciences, Umeå University, Umeå, Sweden;Show MeSH
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Mentions: The experimental design, including the treatment period and the time at which the behavioral tests were conducted in the two experimental models, is shown in Fig. 1.
Affiliation: Umecrine Cognition AB, Solna, Sweden; Umeå Neurosteroid Research Center, Department of Clinical Sciences, Umeå University, Umeå, Sweden;