Combination with non-selective MAO inhibitors might be dangerous.Due to its affinity to the liver enzyme CYP2C9, interactions with drugs being metabolised by this enzyme are also possible, but unlikely. No interaction with tolbutamide, a 2C9 substrate, was observed in studies. Pharmacology
Mechanism of action
Tolcapone selectively and reversibly binds to the catalytic site of COMT in both the periphery and the central nervous system (CNS) with greater affinity than any of the three catecholamines, including levodopa. It thereby prevents the 3-O-methylation of levodopa by COMT in the periphery, which produces 3-O-methyldopa, a major metabolite that competes with levodopa to cross the blood–brain barrier. More of the levodopa that is administered reaches the CNS. Additionally, levodopa that has already reached the CNS, after being converted to dopamine, will not be degraded as quickly when tolcapone inhibits COMT activity. Thus, tolcapone improves the bioavailability and reduces the clearance of levodopa and subsequently dopamine from the CNS. The strength of the binding affinity of tolcapone, represented by the inhibition constant Ki (2.5 nM), can be thought of as the dissociation constant for enzyme and inhibitor complex kinetics. Maximum catalytic activity denotes the efficacy of tolcapone (Vmax = 58.4 pmol/min·mg). Pharmacokinetics
Tolcapone is quickly absorbed from the gut to about 85%. It has an absolute bioavailability of 65%, which is only slightly decreased when taken with food. The substance reaches highest blood plasma concentrations after about two hours. When in the bloodstream, it is almost completely (>99.9%) bound to plasma proteins, primarily albumin.
Around 25% of people (1.8 billion globally) are currently affected. Signs and symptoms
The first symptoms most people notice are difficulty reading fine print, particularly in low light conditions, eyestrain when reading for long periods, blurring of near objects or temporarily blurred vision when changing the viewing distance. Many extreme presbyopes complain that their arms have become "too short" to hold reading material at a comfortable distance.Presbyopia, like other focal imperfections, becomes less noticeable in bright sunlight when the pupil becomes smaller. As with any lens, increasing the focal ratio of the lens increases depth of field by reducing the level of blur of out-of-focus objects (compare the effect of aperture on depth of field in photography). The onset of presbyopia varies among those with certain professions and those with miotic pupils. In particular, farmers and homemakers seek correction later, whereas service workers and construction workers seek correction earlier. Scuba divers with interest in underwater photography may notice presbyopic changes while diving before they recognize the symptoms in their normal routines due to the near focus in low light conditions. Interaction with myopia
People with low near-sightedness can read comfortably without eyeglasses or contact lenses even after age forty, but higher myopes might require two pairs of glasses (one for distance, one for near), bifocal, or progressive lenses. However, their myopia does not disappear and the long-distance visual challenges remain.