['Recurrent hypoglycaemia leads to an attenuation of hypoglycaemic symptoms and hormonal counterregulatory responses. This phenomenon poses a severe problem in the treatment of patients with diabetes mellitus, but the underlying neuroendocrine mechanisms are unclear. On the basis of animal experimental findings, we hypothesized that counterregulatory attenuation represents a basic adaptive learning process relying on synaptic long-term potentiation or depression. If so, attenuation should be prevented by blocking glutamatergic N-methyl-D-aspartate (NMDA) receptors.', 'Sixteen healthy young men participated in two conditions, separated by 4\u2009weeks. Participants received the NMDA antagonist memantine over 5\u2009days (15\u2009mg/day) in one condition and placebo in the other one. After 3\u2009days of drug administration, participants underwent two hypoglycaemic clamps on day 4 and another one on day 5. We assessed blood concentrations of counterregulatory hormones (cortisol, ACTH, epinephrine, norepinephrine, growth hormone and glucagon) as well as subjective symptoms of hypoglycaemia and word-list recall as an indicator of short-term memory.', 'Counterregulatory responses of all hormones as well as neuroglycopenic and autonomic symptom ratings showed robust attenuation following the third as compared to the first hypoglycaemia (p\u2009<\u20090.05). NMDA receptor antagonization by memantine impaired memory function but did not alter any neuroendocrine measure of counterregulatory attenuation (p > 0.17).'] Does nMDA receptor blockade by memantine prevent adaptation to recurrent hypoglycaemia in healthy men?