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  • Title: Selectivity of MDL 72,974A for MAO-B inhibition based on substrate and metabolite concentrations in plasma.
    Author: Huebert ND, Schwach V, Hinze C, Haegele KD.
    Journal: Prog Brain Res; 1995; 106():135-42. PubMed ID: 8584649.
    Abstract:
    Plasma concentrations of 3,4-dihydroxyphenylethylglycol (DOPEG), noradrenaline (NA), adrenaline (A), 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA) and phenylethylamine (PEA) were analyzed in samples taken prior to, during and following the administration of single, daily doses of 12 or 24 mg MDL 72,974A to healthy male volunteers. No effects on the concentrations of DOPA, A, DA or DOPAC were seen during the administration of either dose over 10 days. No treatment-related changes in the concentration of NA were evident at either dose. No changes in DOPEG or PEA concentrations were seen with the 12 mg dose; however, small but significant decreases in plasma DOPEG concentrations and a significant increase in PEA were seen during the administration of the 24 mg dose. This would suggest that at the 24 mg dose some intraneuronal inhibition of MAO-A may be occurring although the lack of increases in NA and A concentrations indicates no accompanying change in sympatho-adrenal activity. Plasma PEA concentrations do not provide a more sensitive or functional indication of MAO-B inhibition. The increase in PEA concentrations at the higher dose may suggest that the inhibition of both forms of the enzyme is necessary to increase its plasma concentration.
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