Minor effect of tolcapone, a catechol-O-methyltransferase inhibitor, on extracellular dopamine levels modified by amphetamine or pargyline: a microdialysis study in anaesthetized rats.
In vivo microdialysis was used to examine the effects of tolcapone (30 mg/kg) on dopamine metabolism in amphetamine (5 mg/kg) and pargyline (75 mg/kg) treated rats. Amphetamine- or pargyline-induced decreases in the extracellular dihydroxyphenyl acetic acid (DOPAC) levels were counteracted by additional tolcapone. Tolcapone also decreased homovanillic acid effluxes below those caused by amphetamine or pargyline. However, dopamine effluxes were not further enhanced by additional tolcapone. These results show that central metabolism of dopamine can be modulated by catechol-O-methyltransferase (COMT) inhibition also without exogenous L-DOPA. However, extracellular dopamine levels are not easily increased.
Tuomainen
P
P
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Törnwall
M
M
Männistö
P T
PT
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000768:Anesthesia, General; D000818:Animals; D001577:Benzophenones / Q000494:pharmacology*; D065098:Catechol O-Methyltransferase Inhibitors; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009596:Nitrophenols; D010293:Pargyline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077867:Tolcapone
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D009596:Nitrophenols; D015102:3,4-Dihydroxyphenylacetic Acid; D010293:Pargyline; D000077867:Tolcapone; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid