Studies on the biochemical mode of action of EGYT-475, a new antidepressant.

Abstract

We studied the mode of action of N-benzyl-piperazine-picolinylfumarate (EGYT-475) and of its metabolite N-benzyl-piperazine (EGYT-2760) in CFY rats. It was found that EGYT-475 had no uptake-inhibitory effect but EGYT-2760 inhibited the high-affinity uptake of 3H-noradrenaline, 3H-dopamine and especially that of 3H-serotonin both in vitro and ex vivo. Neither of the two compounds changed the serotonin turnover. Only EGYT-2760 evoked hyperthermia in rats at a high ambient temperature (28 degrees C). This effect was abolished by cyproheptadine but not by amitriptyline. EGYT-2760 antagonized serotonin-induced contractions of the stomach fundus but it was inactive in inhibiting the serotonin-induced platelet aggregation. Our results suggest that EGYT-2760, an active metabolite of EGYT-475, has a central serotoninomimetic action which involves 5-HT uptake-inhibition and 5-HT1 receptor agonistic effect.

• Authors: K Tekes, L Tóthfalusi, B Malomvölgyi, F Hermán, K Magyar
• Journal: Polish journal of pharmacology and pharmacy (Pol J Pharmacol Pharm) 1987 Mar-Apr Vol. 39 Issue 2 Pg. 203-11 ISSN: 0301-0244 [Print] Poland
• PMID: 2448760 (Publication Type: Journal Article)

Chemical References

• Antidepressive Agents
• Piperazines
• Prostaglandins F
• Serotonin
• EGYT 475
• 1-benzylpiperazine
• Hydroxyindoleacetic Acid
• Dinoprost

Topics

• Animals
• Antidepressive Agents (pharmacology)
• Body Temperature (drug effects)
• Brain (drug effects, metabolism)
• Chromatography, High Pressure Liquid
• Dinoprost
• Gastric Mucosa (metabolism)
• Humans
• Hydroxyindoleacetic Acid (metabolism)
• In Vitro Techniques
• Piperazines (pharmacology)
• Platelet Aggregation (drug effects)
• Prostaglandins F (metabolism)
• Rats
• Serotonin (metabolism, physiology)
• Stomach (drug effects)