Comparison of two new inhibitors of catechol O-methylation on striatal dopamine metabolism: a microdialysis study in rats
| Autor: | Ants Kask, Pekka T. Männistö, Seppo Kaakkola, M. Törnwall, Päivi Tuomainen |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
Microdialysis 3 4-Dihydroxyphenylacetic acid Pyridones Dopamine Amidines Catechols Pharmacology COMT inhibitor Levodopa Stereotaxic Techniques 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Nitriles medicine Animals Biogenic Monoamines Entacapone Rats Wistar 030304 developmental biology 0303 health sciences Catechol-O-methyl transferase Homovanillic acid Tryptophan Carbidopa Catechol O-Methyltransferase Inhibitors Homovanillic Acid Hydroxyindoleacetic Acid Rats Neostriatum chemistry Stereotaxic technique 3 4-Dihydroxyphenylacetic Acid Tyrosine sense organs 030217 neurology & neurosurgery Research Article medicine.drug |
| Zdroj: | British Journal of Pharmacology. 112:13-18 |
| ISSN: | 0007-1188 |
| DOI: | 10.1111/j.1476-5381.1994.tb13021.x |
| Popis: | 1. 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. 2. 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%. 3. 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. 4. 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). 5. 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%). 6. 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. |
| Databáze: | OpenAIRE |
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