The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia.

Aims/hypothesis: Our hypothesis is that reducing release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with modafinil will enhance symptomatic and hormonal responses to hypoglycaemia.

Methods: Nine healthy men received, in random order, two 100-mg doses of modafinil or placebo, followed by an insulin clamp in which plasma glucose was either reduced stepwise to 2.4 mmol/l or was sustained at euglycaemia (four studies). Catecholamines, symptom scores and cognitive function were measured.

Results: Modafinil had no effect on the measured parameters during euglycaemia. During hypoglycaemia, autonomic symptom scores were significantly higher with modafinil (increase at lowest plasma glucose concentration 271.3+/-118.9 vs 211.2+/-80.4/40 min, p=0.019), and the heart rate response was increased (12,928+/-184 vs 6773+/-148 bpm/140 min, p=0.016). Deterioration in performance of two cognitive tasks was reduced: Stroop colour-word test (613+/-204 vs 2375+/-161/65 min, p=0.009) and accuracy of a simple reaction task (11.3+/-1.8 vs 9.4+/-3.7, p=0.039).

Conclusions/interpretation: We conclude that modafinil improves adrenergic sensitivity and some aspects of cognitive function at hypoglycaemia, possibly by reducing neuronal central GABA concentrations.