title: Comparison of serotonin agonistic and antagonistic activities of a new antidepressant agent Trelibet (EGYT-475) and its metabolite EGYT-2760 on isolated rat fundus.
abstract: The effects of Trelibet (EGYT-475, N-benzyl-piperazine-picolinyl-fumarate) and its active metabolite (EGYT-2760, N-benzyl-piperazine) on the serotoninergic responses of rat stomach fundus were investigated and compared with those of MCPP (m-chlorophenyl-piperazine) which is the common metabolite of the arylpiperazine antidepressants Trazodone and Etoperidone. The contraction inhibitory potencies of the agents were determined on the equipotent contractions (EC50) to serotonin (5-HT) and prostaglandin F2 alpha (PGF2 alpha). Isotonic contractile responses to 5-HT were not affected by EGYT-475, however, both EGYT-2760 and MCPP produced concentration related and reversible inhibition of the serotoninergic responses. The IC50 values for EGYT-2760 and MCPP were 40.5 +/- 7.5 mumol/l and 125 +/- 35 nmol/l, respectively. The inhibition was selective for the serotoninergic responses, as the equipotent responses to PGF2 alpha were not affected. EGYT-2760 and MCPP displayed not only 5-HT antagonistic, but also partial agonistic activities on the rat fundus preparation. Maximum contractile response of the fundus preparation to MCPP was approximately 25%, to EGYT-2760 was 10% of the maximum response to 5-HT.
authors.affiliation: Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Malomvölgyi
authors.forename: L
authors.initials: L
authors.lastname: Tóthfalusi
authors.forename: K
authors.initials: K
authors.lastname: Tekes
authors.forename: K
authors.initials: K
authors.lastname: Magyar
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D007551:Isotonic Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D012702:Serotonin Antagonists; D012701:Serotonin; C040401:EGYT 475; C006737:1-benzylpiperazine; D015237:Dinoprost; C015068:1-(3-chlorophenyl)piperazine