NMDA receptor antagonist memantine increases neuroglycopenic symptoms during hypoglycaemia

Introduction: Glutamate signaling at the NMDA receptor is involved in the regulation of neuroendocrine secretion. We have previously shown that hormonal counterregulation during hypoglycaemia is enhanced by the NMDA antagonist memantine. Here we examined the effect of memantine on subjective symptoms and aspects of cognitive function during hypoglycaemia. Methods: Two hypoglycaemic clamp experiments were performed in 10 subjects, once after oral administration of 20mg memantine and another time after placebo. Neuroglycopenic and autonomic symptoms were assessed before and during hypoglycaemia. We also evaluated aspects of cognitive function (short-term memory and attention) throughout the experiment. Results: In the memantine condition, neuroglycopenic symptoms were enhanced during hypoglycaemia in comparison to placebo. Also, there was a trend towards increased autonomic symptoms during hypoglycaemia after memantine. In particular, rated hunger during the hypoglycaemic plateau was enhanced by memantine. The assessed cognitive functions were not influenced by memantine administration. Conclusion: Pretreatment with the NMDA antagonist memantine enhances neuroglycopenic symptoms and hunger during hypoglycaemia while aspects of cognitive function remain unchanged. Results support the assumption of an involvement of glutamate signalling at the NMDA receptor in neuroendocrine counterregulation and subjective symptom perception during hypoglycaemia. Our findings might be of clinical relevance in patients with diabetes suffering from hypoglycaemia unawareness because memantine might improve the perception of hypoglycaemic episodes.