Extending levodopa action: COMT inhibition.
Degradation of levodopa in the periphery is known to be associated with motor fluctuations and dyskinesia in Parkinson's disease (PD) patients. The enzyme catechol-O-methyltransferase (COMT) is responsible for much of this degradation. Therefore, inhibiting COMT activity is one method of extending the action of levodopa. The new nitrocatechol-type COMT inhibitors entacapone, nitecapone, and tolcapone inhibit COMT in the periphery; tolcapone also inhibits COMT activity centrally. COMT inhibitors increase patients' duration of response to levodopa and reduce response fluctuations. Administration may prolong levodopa-induced dyskinesia, but peak-dose dyskinesia does not appear to increase. To reduce dyskinesia, the total daily dose of levodopa can be reduced.
Martínez-Martín
P
P
Department of Neurology, Hospital Universitario de Getafe, Madrid, Spain.
O'Brien
C F
CF
D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001577:Benzophenones / Q000008:administration & dosage / Q000009:adverse effects; D002394:Catechol O-Methyltransferase / Q000502:physiology; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D009570:Nitriles; D009596:Nitrophenols; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D010422:Pentanones / Q000008:administration & dosage / Q000009:adverse effects; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D009596:Nitrophenols; D010422:Pentanones; D007980:Levodopa; C071192:entacapone; C057364:nitecapone; D000077867:Tolcapone; D002394:Catechol O-Methyltransferase