Methylene blue is a thiazine dye that increases the conversion of methemoglobin to hemoglobin. Methylene blue is reduced via methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue, which in turn reduces methemoglobin. Glucose-6-phospate dehydrogenase (G6PD) is essential for the generation of NADPH and is thus essential for the function of methylene blue as an antidote. Therapeutic effect is seen within 30 minutes. Methemoglobin is excreted in bile and urine, which may turn blue or green.
Methylene blue has been used to treat ifosfamide-induced encephalopathy, but the exact pathophysiologic mechanisms responsible are not known. Methylene blue may reverse the neurotoxic effects of the ifosfamide metabolites.
Methylene blue, as a guanylate cyclase inhibitor, reduces cyclic guanosine monophosphate (cGMP) production and nitric oxide (NO) stimulation. Excessive NO activity may contribute to refractory vasodilatory shock associated with sepsis, vasoplegia following cardiac surgery, anaphylactic shock, and metformin and amlodipine toxicity. Methylene blue has been used to improve hemodynamics in each of these circumstances.
Methylene blue is an MAO-A inhibitor and has been responsible for the precipitation of a serotonin syndrome in patients treated with selective serotonin reuptake inhibitors (SSRIs) when used for cardiac and parathyroid surgery.