Effects of three types of catechol O-methylation inhibitors on L-3,4-dihydroxyphenylalanine-induced circling behaviour in rats

Abstract

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 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.