Pharmacological characterization of LB50016, N-(4-amino)butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist.
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.
Lee
C H
CH
Department of Pharmacology, Hanyang University, College of Medicine, Seoul, Korea.
Oh
J I
JI
Park
H D
HD
Kim
H J
HJ
Park
T K
TK
Kim
J S
JS
Hong
C Y
CY
Lee
S J
SJ
Ahn
K H
KH
Kim
Y Z
YZ
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*
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