title: Pharmacological characterization of LB50016, N-(4-amino)butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist.
abstract: LB50016 was characterized as a selective and potent 5-HT1A receptor agonist and evaluate its anxiolytic and antidepressant activities. It shows high affinity for 5-HT1A receptor, moderate affinity for alpha 2 adrenergic and 5-HT2A receptors and no significant affinity for other receptors tested. Hypothermia and increased serum corticosterone level were observed in LB50016-treated rats, which are mediated mostly by post synaptic 5-HT1A receptor activation. In the mouse forced swim model for depression, LB50016-elicited dose-dependent reductions in immobility time, showing ED50 of approximately 3 mg/kg i.p., which was blocked by pretreatment of NAN-190, 5-HT1A antagonist. In face-to-face test for anxiolytic activity in mice, estimated ED50 was 2 mg/kg, i.p. In isolation-induced aggression test with mice, fifty-fold increases in latency to attack were observed at 30 min and last up to 4 h after LB50016 treatment (3 mg/kg, i.p.). Taken together, LB50016-induced pharmacological activities are mediated by activation of 5-HT1A receptors, offering an effective therapeutic candidate in the management of anxiety and depression in humans.
authors.affiliation: Department of Pharmacology, Hanyang University, College of Medicine, Seoul, Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Lee
authors.forename: J I
authors.initials: JI
authors.lastname: Oh
authors.forename: H D
authors.initials: HD
authors.lastname: Park
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: T K
authors.initials: TK
authors.lastname: Park
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: C Y
authors.initials: CY
authors.lastname: Hong
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Ahn
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Kim
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000374:Aggression / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003499:Cyclic S-Oxides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D003499:Cyclic S-Oxides; C119614:LB 50016; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone