GTN administration induces an increase in nNOS that is simultaneous with a hyperalgesic condition and neuronal activation in brain areas involved in migraine pain [38, 39], thus suggesting that NOS inhibition may be a potential therapeutic target for migraine. Experimental and clinical studies suggest that NOS inhibition influences the activation of the trigeminal vascular system and that nonselective NOS inhibition is associated to antimigraine activity [40, 41]. Clinical application of non selelctive NOS inhibition is however hindered by the cardiovascular effects, i.e., increase of mean arterial pressure and a decrease of heart rate for its pharmacokinetic profile [41].