Effect of MAO inhibitors on the uptake and metabolism of dopamine in rat and human brain.
Complex pharmacological effect of l-deprenyl cannot be explained by its MAO-B inhibitory action only. In contrast to other parent MAO inhibitors (J-512, J-516, LK-63, U-1424) l-, and d-deprenyl inhibit the hypothalamic noradrenaline and striatal dopamine (DA) reuptake without influencing the uptake of serotonin, both in rat and in human brain. Long-term treatment 19 x 0.25 mg/kg or 0.5 mg/kg, sc with l-deprenyl elicits 37 +/- 2.8 and 43 +/- 3.2% inhibition, respectively, of DA reuptake capacity in the rat striatal cell-free homogenate. To compare the potencies of deprenyl isomers on DA and DOPAC levels of rat striatum drugs were given 0.25, 2 and 8 mg/kg ip and their effects measured 4 and 48 h after treatment. DA content was increased only by 8 mg/kg d-deprenyl 4 h after its injection, but DOPAC level was decreased by both isomers. After 48 h, actions of d-deprenyl terminated but the effect of l-deprenyl was still present.
Tekes
K
K
Department of Pharmacodynamics, Semmelweis Medical School, Budapest, Hungary.
Tóthfalusi
L
L
Gaál
J
J
Magyar
K
K
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D000661:Amphetamine; D003010:Clorgyline; D004298:Dopamine