The effect of EGYT-475 (Trelibet) and its metabolites on the potassium-stimulated 3H-noradrenaline release from cortical slices of rat brain.
The effect of a new antidepressant drug: EGYT-475 (Trelibet) and its metabolites: EGYT-1354 and EGYT-2760 on the K+-stimulated overflow of 3H-noradrenaline from rat brain cortical slices was studied. The parent compound and EGYT-1354 were ineffective at a concentration of 10(-4) mole/l but EGYT-2760 increased both the spontaneous and the potassium-evoked tritium release in the concentration range of 10(-8)-10(-5) mole/l. The increasing effect of EGYT-2760 on the basal tritium outflow was similar to that of D-amphetamine: it could be prevented by neuronal uptake inhibitors (cocaine and desipramine) and did not depend on the extracellular Ca++ concentration. EGYT-2760 and D-amphetamine enhanced the K+-induced 3H-noradrenaline overflow too, however this effect of D-amphetamine was abolished in the presence of cocaine and desipramine, while the effect of EGYT-2760 remained unaffected. EGYT-2760 did not possess presynaptic alpha 2-adrenoceptor antagonist property: it could not antagonize the inhibitory effect of clonidine.
Szücks
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Z
EGIS Pharmaceuticals, Biochemical Department, Budapest, Hungary.
Szentendrei
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Fekete
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MI
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000928:Antidepressive Agents; D010879:Piperazines; C040401:EGYT 475; D003000:Clonidine; D011188:Potassium; D002118:Calcium; D003913:Dextroamphetamine; D009638:Norepinephrine