Effect of amperozide on the synthesis and turnover of monoamines in rat brain.
The effects of amperozide on the synthesis and the turnover of monoamines in different brain regions of the rat were determined using both ex vivo and in vivo biochemical techniques (i.e. post-mortem measurements of the tissue levels by HPLC-EC, and direct measurements with the in vivo voltammetry technique). It was found that amperozide slightly increased the DOPA accumulation and the DOPAC content in limbic brain areas but not in the striatum. The DOPA accumulation was also slightly increased in the noradrenaline rich cortical region indicating increased synthesis of noradrenaline. Furthermore, amperozide increased the utilization of noradrenaline after tyrosine hydroxylase inhibition by alpha-methyl-p-tyrosine. The synthesis of 5-HT was not significantly altered by amperozide. In conclusion, the biochemical data obtained in this study suggest that amperozide produces preferential effects on the mesolimbic dopaminergic system. In addition, amperozide also interacts with the noradrenergic system.
Pettersson
G
G
Dept. of CNS-Research, Pharmacia LEO Therapeutics AB, Malmö, Sweden.
Johannessen
K
K
Hulthe
P
P
Engel
J A
JA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000096:biosynthesis / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D019805:alpha-Methyltyrosine
D015306:Biogenic Monoamines; D008781:Methyltyrosines; D010879:Piperazines; D011619:Psychotropic Drugs; C049058:amperozide; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D019805:alpha-Methyltyrosine; D006916:5-Hydroxytryptophan; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid