Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations.

摘要: Background and purpose:  There is increasing evidence that not only the monoaminergic but also glutamatergic system involved in pathophysiology of attention-deficit hyperactivity disorder (ADHD). Hyperactivity glutamate metabolism might be causally related to a hypoactive state dopaminergic system. Atomoxetine, selective noradrenaline reuptake inhibitor, first non-stimulant approved for treatment this disorder. Here we have evaluated effects atomoxetine on receptors vitro. Experimental approach:  The whole-cell configuration patch-clamp technique was used analyse effect N-methyl-d-aspartate (NMDA) cultured rodent cortical hippocampal neurons as well NMDA heterologously expressed human TsA cells. Key results:  Atomoxetine blocked NMDA-induced membrane currents. Half-maximal inhibition emerged at about 3 µM which range clinically relevant concentrations found plasma patients treated with drug. voltage-dependent, indicating an open-channel blocking mechanism. Furthermore, inhibitory potency did vary when measured from different brain regions or subunit compositions. Conclusions implications:  effective receptor antagonism by low micromolar may its clinical ADHD. Our data provide further altered transmission play role ADHD pathophysiology.