Chronic effects of tranylcypromine and 4-fluorotranylcypromine on regional brain monoamine metabolism in rats: a comparison with clorgyline.
A regional analysis of brain amine and acid metabolite levels was conducted after chronic administration of the antidepressant tranylcypromine (0.5 mg/kg/day), of a novel fluorinated analog of this compound, and of clorgyline (1.0 mg/kg/day). These compounds were administered to male Sprague-Dawley rats for 28 days by subcutaneous infusion using osmotic minipumps (Alzet 2002). Levels of noradrenaline, 5-hydroxytryptamine, dopamine, and of the acid metabolites 5-hydroxyindole-3-acetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in the frontal cortex, nucleus accumbens, caudate nucleus, hippocampus, and hypothalamus. After 28 days of drug administration, sustained increases in amines and decreases in their acid metabolites were observed. Regional differences in these effects were minimal. These results are consistent with reports of sustained increases in brain amine concentrations following prolonged administration of other monoamine oxidase inhibitors.
Greenshaw
A J
AJ
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Rao
T S
TS
Nazarali
A J
AJ
Baker
G B
GB
Coutts
R T
RT
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D003010:Clorgyline / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014191:Tranylcypromine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D018377:Neurotransmitter Agents; D011437:Propylamines; D015102:3,4-Dihydroxyphenylacetic Acid; C055203:4-fluorotranylcypromine; D012701:Serotonin; D014191:Tranylcypromine; D006897:Hydroxyindoleacetic Acid; D003010:Clorgyline; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid