TMU4142 is a selective 5-HT 1a agonist with high GoA activity. TMU4142 has weak Gi3 activity, can elicit rapid antidepressant like effects without triggering significant activation of dorsal raphe nucleus (DRN) 5-HT 1a R autoreceptors or serotonergic neuron firing. TMU4142 demonstrates fast-acting efficacy in mouse models of depression. TMU4142 can be used for antidepressants research [1].
In Vivo, TMU414 (0.3 or 1.5 mg/kg, i.p.) has GoA-biased with minimal Gi3 activity, selectively activates the GoA signaling pathway (primarily localized postsynaptically and antidepressant responses) while avoiding the Gi3-mediated feedback of presynaptic autoreceptors, preserves 5-HT synthesis and release in the DRN in chronic restraint stress-induced depression model in C57BL/6 mice[1].
In Vitro, TMU4142 agonist GoA signaling pathway and weak activity at the Gi3 pathway, shows no discernible activity at the β-arrestin-2 pathway associated with the 5-HT1a receptor, demonstrates a higher potency at the 5-HT1a receptor while reducing activity at β-adrenergic receptors[1].
References:
[1]. Wang C, et al. Pathway-selective 5-HT1AR agonist as a rapid antidepressant strategy. Cell. 2025 Dec 11;188(25):7222-7237.e24.
In Vivo, TMU414 (0.3 or 1.5 mg/kg, i.p.) has GoA-biased with minimal Gi3 activity, selectively activates the GoA signaling pathway (primarily localized postsynaptically and antidepressant responses) while avoiding the Gi3-mediated feedback of presynaptic autoreceptors, preserves 5-HT synthesis and release in the DRN in chronic restraint stress-induced depression model in C57BL/6 mice[1].
In Vitro, TMU4142 agonist GoA signaling pathway and weak activity at the Gi3 pathway, shows no discernible activity at the β-arrestin-2 pathway associated with the 5-HT1a receptor, demonstrates a higher potency at the 5-HT1a receptor while reducing activity at β-adrenergic receptors[1].
References:
[1]. Wang C, et al. Pathway-selective 5-HT1AR agonist as a rapid antidepressant strategy. Cell. 2025 Dec 11;188(25):7222-7237.e24.