Effects of CGP 28014 on the in vivo release and metabolism of dopamine in the rat striatum assessed by brain microdialysis.
The effects on rat striatal dopamine (DA) metabolism of systemic and local administration of CGP 28014, an inhibitor of catechol-O-methyl-transferase (COMT), were studied by in vivo microdialysis. CGP 28014 (30 mg/kg i.p.) significantly reduced the levels of homovanillic acid (HVA), but did not modify DA and 3,4-dihydroxyphenylacetic acid (DOPAC). The intrastriatal administration (via the microdialysis probe) of 5, 7.5, 10, and 20 mM of CGP 28014 elicited a concentration-dependent, several-fold increase in extracellular DA but did not alter the levels of HVA and DOPAC. Thus, the effects of CGP 28014 observed after i.p. injection (decrease in HVA levels) are different from those measured after intrastriatal administration (increase in DA release). Therefore, the inhibition of COMT is likely to be due to the action of a metabolite of CGP 28014 formed in the periphery and not in the brain.
Steulet
A F
AF
Research Department, Pharmaceuticals Division, CIBA-GEIGY Ltd., Basel, Switzerland.
Stöcklin
K
K
Wicki
P
P
Waldmeier
P
P
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000578:Amidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D006719:Homovanillic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D009596:Nitrophenols; D010537:Peritoneum; D011728:Pyridones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D000077867:Tolcapone
D000578:Amidines; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D009596:Nitrophenols; D011728:Pyridones; D015102:3,4-Dihydroxyphenylacetic Acid; C067181:N-(2-pyridone-6-yl)-N',N'-di-n-propylformamidine; D000077867:Tolcapone; D004298:Dopamine; D006719:Homovanillic Acid