Effect of nitecapone and clorgyline, given intracerebro-ventricularly on L-dopa metabolism in the rat brain.
A new COMT inhibitor, nitecapone (OR-462) or clorgyline, a MAO-A inhibitor, was infused into the 3rd brain ventricle (i.c.v.) of conscious male rats. None of the enzyme inhibitors given alone alter hypothalamic or striatal levels of L-dopa, dopamine or their metabolites. Most of the rats were pretreated with levodopa/carbidopa (LD/CD, 15/30 mg kg-1 intraperitoneally). Now, the action of nitecapone is localized in the hypothalamus since homovanillic acid (HVA) is decreased there, not in the striatum. The levels of 3-O-methyldopa (3-OMD) are not changed in either brain region, suggesting a lack of the peripheral leakage of nitecapone. Clorgyline (3 and 10 micrograms rat-1) elevates hypothalamic and dopamine levels. Nitecapone and clorgyline decrease prolactin (PRL) levels below those reduced by LD/CD treatment.
Männistö
P T
PT
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Törnwall
M
M
Tuomainen
P
P
Borisenko
S A
SA
Tuominen
R K
RK
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002230:Carbidopa / Q000494:pharmacology; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003010:Clorgyline / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D007980:Levodopa / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010422:Pentanones / Q000008:administration & dosage / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood*
D002396:Catechols; D010422:Pentanones; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D011388:Prolactin; D013972:Thyrotropin; C057364:nitecapone; D003010:Clorgyline; C035420:levodopa methyl ester; D002230:Carbidopa; D004298:Dopamine; D006719:Homovanillic Acid