The effects of 5-hydroxy-5(4'-chlorophenyl)-2, 3-dihydro-5H-imidazo (2, 1-a) isoindole (mazindol, SaH 42-548) on the metabolism of brain norepinephrine.
Mazindol, 5-hydroxy-5-(4'-chlorophenyl)-i, 3-dihydro-5H-imidazo-(2, 1-a) isoindole, has demonstrated anorexic activity and other pharmacological responses which suggest alterations in brain norepinephrine metabolism. Studies of the effects of mazindol on neuronal uptake and/or release of norepinephrine showed that mazindol, when given before cerebral intraventricular injection of 3-H-norepinephrine by a mechanism that increases 3-H-normetanephrine synthesis via catechol-O-methyl-transferase and provided no significant effect on deamination of the catecholamine. Studies designed to measure norepinephrine release showed that mazindol (in contrast to d-amphetamine) did not cause release of 3-H-norepinephrine from neuronal stores. Furthermore, mazindol did not inhibit norepinephrine synthesis, whereas d-amphetamine did. The effect of d-amphetamine on norepinephrine release and synthesis may be more important than effects on uptake of this catecholamine. In contrast, mazindol appears to produce its primary effect on norepinephrine metabolism by inhibition of neuronal uptake mechanism.
D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D003641:Deamination; D003913:Dextroamphetamine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D009647:Normetanephrine; D008454:Mazindol; D002394:Catechol O-Methyltransferase; D003913:Dextroamphetamine; D009638:Norepinephrine