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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

Cell culture Human MM cell lines MM.1S, RPMI-8226, U266 and NCI-H929 were from ATCC (Manassas, VA, USA) and MOLP-2, KMS-12-PE, OPM-2 and EJM were from DSMZ (Braunschweig, Germany)

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The oxime group (=NOH) in pralidoxime or stabilized due to the spontaneous loss of an alkyl group from the organophosphate compound