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10.1016/j.vph.2017.05.005 2 AriannaC.JaskarenK.ElenaZ.PellegriniL.DemariaM.AlimontiA

Proposed Mechanisms Preventing GABA receptor downregulation Counteracting compensatory NMDA glutamate receptor sensitization Stabilizing benzodiazepine receptor configuration (preventing shift to inverse agonist state) Upregulating GABAergic neurotransmission through pathways distinct from benzodiazepine action itself This tolerance prevention has profound clinical implications

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Following the current meetings, the committees recommendations are non-binding but are expected to inform the FDAs final decision on whether to allow the peptides to the agencys list of permitted bulk drug substances for compounding