Article date: May 1994
By: M. Törnwall, S. Kaakkola, P. Tuomainen, A. Kask, P.T. Männistö, in Volume 112, Issue 1, pages 13-18
Effects of two new inhibitors of catechol O‐methylation (CGP 28014 and entacapone; 30 mg kg−1, i.p.) were compared by means of brain microdialysis in rats treated with l‐3,4‐dihydroxyphenylalanine (l‐dopa)/carbidopa (50/50 mg kg−1, i.p., respectively) or saline.
In saline‐treated rats, CGP 28014 maximally (max) increased striatal dopamine and 3,4‐dihydroxyphenylacetic acid (DOPAC) effluxes by 41% and 49%, respectively, whereas homovanillic acid (HVA) levels were decreased by 71%.
In the presence of l‐dopa/carbidopa, a peripherally active inhibitor of catechol O‐methyltransferase (COMT) entacapone had a short‐lasting increasing effect on l‐dopa efflux. Compared to the effects of l‐dopa/carbidopa alone 3‐O‐methyldopa (3‐OMD) levels were effectively reduced (max 79%) by entacapone, but not by CGP 28014.
Entacapone, in contrast to CGP 28014, increased striatal dopamine efflux (max 492% of that after l‐dopa/carbidopa alone). Also DOPAC levels were increased by entacapone (255% at 180 min), but not significantly by CGP 28014 (159% at 180 min).
Both compounds initially decreased HVA efflux. The effect of CGP 18014 was longer‐lasting. By the end of the measurement, entacapone even increased HVA levels (max 259%).
Our results demonstrate that entacapone is a peripheral COMT inhibitor and support the view that CGP 18014 is mainly a centrally acting inhibitor of O‐methylation.
Effects of two new inhibitors of catechol O‐methylation (CGP 28014 and entacapone; 30 mg kg−1, i.p.) were compared by means of brain microdialysis in rats treated with l‐3,4‐dihydroxyphenylalanine (l‐dopa)/carbidopa (50/50 mg kg−1, i.p., respectively) or saline.
In saline‐treated rats, CGP 28014 maximally (max) increased striatal dopamine and 3,4‐dihydroxyphenylacetic acid (DOPAC) effluxes by 41% and 49%, respectively, whereas homovanillic acid (HVA) levels were decreased by 71%.
In the presence of l‐dopa/carbidopa, a peripherally active inhibitor of catechol O‐methyltransferase (COMT) entacapone had a short‐lasting increasing effect on l‐dopa efflux. Compared to the effects of l‐dopa/carbidopa alone 3‐O‐methyldopa (3‐OMD) levels were effectively reduced (max 79%) by entacapone, but not by CGP 28014.
Entacapone, in contrast to CGP 28014, increased striatal dopamine efflux (max 492% of that after l‐dopa/carbidopa alone). Also DOPAC levels were increased by entacapone (255% at 180 min), but not significantly by CGP 28014 (159% at 180 min).
Both compounds initially decreased HVA efflux. The effect of CGP 18014 was longer‐lasting. By the end of the measurement, entacapone even increased HVA levels (max 259%).
Our results demonstrate that entacapone is a peripheral COMT inhibitor and support the view that CGP 18014 is mainly a centrally acting inhibitor of O‐methylation.
DOI: 10.1111/j.1476-5381.1994.tb13021.x
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