Effects of three types of catechol O-methylation inhibitors on L-3,4-dihydroxyphenylalanine-induced circling behaviour in rats.
The effects of three new, selective inhibitors of catechol O-methylation were compared regarding their potentiation of L-3,4-dihydroxyphenylalanine (L-dopa)/carbidopa-induced contralateral circling behaviour in male rats. Some studies were also done with amphetamine, which causes ipsilateral turning. A peripherally acting compound, entacapone, a peripherally and centrally acting compound, tolcapone, and an atypical compound, CGP 28014 (3, 10 or 30 mg/kg) increased the effect of L-dopa/carbidopa (2/30 or 5/30 mg/kg) on contralateral circling by 2.0-6.1-fold. Addition of clorgyline (3 mg/kg) did not increase, but rather decreased, the entacapone (3 mg/kg) and L-dopa/carbidopa (2/30 or 5/30 mg/kg)-induced peak circling. Amphetamine (2.5 mg/kg)-induced ipsilateral circling behaviour was not affected by tolcapone (30 mg/kg). We conclude that L-dopa-induced circling behaviour is enhanced and prolonged by all types of catechol O-methyltransferase inhibitors regardless of their brain penetration. The results suggest that catechol O-methylation inhibitors may be beneficial as L-dopa adjuncts in the treatment of patients with Parkinson's disease.
Törnwall
M
M
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Männistö
P T
PT
D000578:Amidines / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001577:Benzophenones / Q000494:pharmacology*; D002230:Carbidopa / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D003010:Clorgyline / Q000494:pharmacology; D004347:Drug Interactions; D004357:Drug Synergism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008745:Methylation; D009570:Nitriles; D009596:Nitrophenols; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077867:Tolcapone
D000578:Amidines; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D009570:Nitriles; D009596:Nitrophenols; D011728:Pyridones; C067181:N-(2-pyridone-6-yl)-N',N'-di-n-propylformamidine; D007980:Levodopa; C071192:entacapone; D000077867:Tolcapone; D000661:Amphetamine; D003010:Clorgyline; D002230:Carbidopa