title: Amperozide, a putative anti-psychotic drug: uptake inhibition and release of dopamine in vitro in the rat brain.
abstract: The effects of amperozide (a diphenylbutylpiperazinecarboxamide derivative) on the uptake and release of 3H-dopamine in vitro were investigated. Amperozide inhibited the amphetamine-stimulated release of dopamine from perfused rat striatal tissue in a dose-dependent manner. With 1 and 10 microM amperozide there was significant inhibition of the amphetamine-stimulated release of dopamine, to 44 and 36% of control. In contrast, 10 microM amperozide significantly strengthened the electrically stimulated release of dopamine from perfused striatal slices. Amperozide 1-10 microM had no significant effect on the potassium-stimulated release of dopamine. 10 microM amperozide also slightly increased the basal release of 3H-dopamine from perfused striatal tissue. These effects on various types of release are similar to those reported for uptake inhibitors (Bowyer et al, 1984). The uptake of dopamine in striatal tissue was inhibited by amperozide with IC50 values of 18 microM for uptake in chopped tissue and 1.0 microM for uptake in synaptosomes. Amperozide also inhibited the uptake of serotonin in synaptosomes from frontal cortex, IC50 = 0.32 microM and the uptake of noradrenaline in cortical synaptosomes, IC50 = 0.78 microM. In conclusion, amperozide shows uptake-inhibiting properties in both release and uptake studies done in vitro on the rat. In the in vivo studies, however, amperozide differs from dopamine uptake inhibitors.
authors.affiliation: Dept of CNS-Research, Pharmacia LEO Therapeutics AB, Malmö, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Eriksson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000633:toxicity; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; C049058:amperozide; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine