Nitecapone (3-(3,4-dihydroxy-5-nitrobenzylidine)-2,4- pentanedione, OR-462) is a selective, short-acting catechol-O-methyltransferase (COMT) inhibitor, whose main site of action is in the gastrointestinal tract. Nitecapone displays in vivo activity in peripheral tissues but does not penetrate the blood-brain barrier. The compound increases mechanical and thermal nociception and reduces neuropathic pain in diabetic rats and in a spinal nerve ligation model. Nitecapone has been shown to have a protective effect against ischemia-reperfusion injury in experimental heart transplantation and in Langendorff preparations. Nitecapone added to cardioplegia solution reduces cardiac neutrophil accumulation and transcoronary neutrophil activation during clinical cardiopulmonary bypass. Reflected by better left ventricular stroke volume, nitecapone treatment may be an additional way of reducing the deleterious effects of neutrophil activation during cardiopulmonary bypass. Nitecapone was patented as an antiparkinsonian agent but was never marketed.