Effect of L-deprenyl, its structural analogues and some monoamine oxidase inhibitors on dopamine uptake.
The effect on dopamine uptake by L-deprenyl, its structural analogues and different types of monoamine oxidase (MAO) inhibitors was investigated. Both direct [3H]dopamine uptake into rat striatal slices and binding of a specific dopamine uptake inhibitor [3H]GBR-12935 were used in the present study. L-Deprenyl exhibits a relatively weak dopamine uptake inhibitory effect in vitro, while D-deprenyl possesses a very potent inhibitory effect. The potent effect of D-deprenyl on dopamine uptake may be responsible, at least in part, for its behavioral effects and abuse liability. L-Methamphetamine, a metabolite of L-deprenyl, does not inhibit [3H]GBR-12935 binding but it reduces the retention of [3H]dopamine in striatal tissues, suggesting that it may enhance dopamine release. The MAO-A inhibitors clorgyline and brofaromine also exhibit dopamine uptake inhibitory effects. Irreversible and reversible MAO-B inhibitors, however, such as pargyline, aliphatic N-methylpropargylamines, Ro 19-6327 and MDL-72974A and MAO-A inhibitor moclobemide do not possess any appreciable inhibitory effects on dopamine uptake. Dopamine uptake is probably unrelated to the pharmacological actions of L-deprenyl.
Fang
J
J
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Yu
P H
PH
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000031:analogs & derivatives* / Q000494:pharmacology*
D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D012642:Selegiline; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D004298:Dopamine