Effect of acute levodopa on brain catecholamines after selective MAO and COMT inhibition in male rats

Journal of Neural Transmission. Parkinson's Disease and Dementia Section
P T MännistoS Kaakkola

Abstract

Interactions between a selective catechol-O-methyltransferase (COMT) inhibitor OR-462 and a monoamine oxidase (MAO)-A inhibitor clorgyline were studied measuring concentrations of L-dopa, dopamine and their metabolites in the rat hypothalamus and striatum after administration of levodopa/carbidopa (15/30 mg/kg i.p.). Part of the experiments were performed in rats pretreated with 6-OH-dopamine (6-OHDA) intracerebroventricularly (i.c.v.) to determine whether changes in dopamine metabolism occurred inside or outside catecholaminergic neurons. OR-462 was an effective COMT inhibitor at the doses 3 and 30 mg/kg i.p. Inhibition of 3-O-methyldopa (3-OMD) formation from L-dopa was reflected in the hypothalamus (45-81% decrease) and striatum (87-88% decrease), since 3-OMD penetrates the blood-brain barrier. Homovanillic acid (HVA) was decreased only in the striatum at 30 mg/kg of OR-462. Clorgyline (8 and 32 mg/kg i.p.) decreased 3,4-dihydroxyphenylacetic acid (DOPAC) formation in the hypothalamus and striatum by 61-91%. When given together, OR-462 and clorgyline elevated hypothalamic dopamine levels 3.2-4.6-fold, but striatal dopamine only 1.3-1.9-fold. The formation of 3-OMD and DOPAC remained suppressed and even brain HVA levels were ...Continue Reading

References

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Citations

May 1, 1995·Movement Disorders : Official Journal of the Movement Disorder Society·T L DavisR S Burns
Jan 1, 1995·Journal of Neural Transmission. General Section·A Fredriksson, T Archer
Jan 1, 1992·Journal of Neural Transmission. Parkinson's Disease and Dementia Section·S KaakkolaP T Männistö
Aug 3, 1993·European Journal of Pharmacology·M TörnwallP T Männistö
Sep 1, 1994·Pharmacology, Biochemistry, and Behavior·P T MännistöT Voronina
May 19, 2000·Parkinsonism & Related Disorders·M HuotariP T Männistö
Mar 1, 1992·British Journal of Pharmacology·P T MännistöR K Tuominen
Jan 1, 1995·Acta Psychiatrica Scandinavica. Supplementum·J P Finberg
May 1, 1990·Pharmacology & Toxicology·P T Männistö, S Kaakkola
Jun 1, 1992·Hypertension·E M MervaalaH Karppanen
Sep 1, 1996·Alcoholism, Clinical and Experimental Research·S N MattsonK L Jones
Feb 19, 2005·Pediatric Research·Alistair G S Philip

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