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  • Title: Effect of acute levodopa on brain catecholamines after selective MAO and COMT inhibition in male rats.
    Author: Männistö PT, Tuomainen P, Toivonen M, Törnwall M, Kaakkola S.
    Journal: J Neural Transm Park Dis Dement Sect; 1990; 2(1):31-43. PubMed ID: 2113389.
    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 decreased by 51-97%. 6-OHDA treatment decreased striatal and hypothalamic dopamine by 50% and noradrenaline by 75%. In these animals levodopa/carbidopa increased brain L-dopa 2.4-4-fold, those of 3-OMD 1.2-1.7-fold compared to intact animals, but the synthesis and metabolism of dopamine and the effects of COMT and MAO inhibitors were not significantly changed. Levodopa/carbidopa treatment decreased significantly prolactin and thyrotropin levels in serum but none of the additional treatments changed this action.
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