Effects of tolcapone in Parkinson's patients taking L-dihydroxyphenylalanine/carbidopa and selegiline.
A double-blind, placebo-controlled, crossover trial of tolcapone (RO 40-7592), a potent reversible inhibitor of catechol-O-methyltransferase (COMT), was performed in 10 Parkinson's disease (PD) patients to determine single-dose safety and efficacy. All subjects were chronically treated with stable doses of selegiline and L-dihydroxyphenylalanine (L-DOPA)/carbidopa. Tolcapone was administered in four single ascending doses (50-800 mg) randomly paired with placebo. Motor ratings were performed every 30 min for 6 h. At higher doses (400 mg and 800 mg), tolcapone prolonged the antiparkinson response of L-DOPA. Nausea was the most common adverse effect of the tolcapone-L-DOPA/carbidopa-selegiline combination. Adverse cardiovascular effects were not seen. The acute inhibition of amino acid decarboxylase, monoamine oxidase-B, and COMT is well tolerated and prolongs the L-DOPA response in PD patients. Tolcapone may be a safe and useful adjunct to L-DOPA/carbidopa in PD patients taking selegiline.
Davis
T L
TL
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennnessee, USA.
Roznoski
M
M
Burns
R S
RS
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001577:Benzophenones / Q000008:administration & dosage* / Q000009:adverse effects; D002230:Carbidopa / Q000008:administration & dosage* / Q000009:adverse effects; D065098:Catechol O-Methyltransferase Inhibitors; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D009596:Nitrophenols; D010300:Parkinson Disease / Q000188:drug therapy*; D012642:Selegiline / Q000008:administration & dosage* / Q000009:adverse effects; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D009596:Nitrophenols; D012642:Selegiline; D007980:Levodopa; D000077867:Tolcapone; D002230:Carbidopa