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Pharmacological characterization of LB50016, N-(4-amino) butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist

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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 α2 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.

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Lee, C.H., Oh, J.I., Park, H.D. et al. Pharmacological characterization of LB50016, N-(4-amino) butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist. Arch Pharm Res 22, 157–164 (1999). https://doi.org/10.1007/BF02976540

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