Serotonin (5-HT) is a chemical mediator synthesized from tryptophan and acts as a neurotransmitter in mammals. Besides, 5-HT is a regulator that regulates neuronal connections during development by regulating cell migration and structure. The 5-HT1A receptor belongs to the serotonin receptor family and is composed of 13 receptor subtypes. Importantly, 5-HT1A receptor plays a crucial role in serotonin neurotransmission. Because it is located both as a presynaptic receptor on the serotonin cell body in the raphe nucleus and as a postsynaptic heterogeneous receptor in the forebrain region that receives serotonin projections. Particularly, the 5-HT1A receptor is involved in various physiological and pathological processes, making it an important therapeutic target in psychiatry and recent neurological diseases. Here, we will introduce a selective 5-HT1A receptor partial agonist for central nervous system disorders research, Tandospirone.

Tandospirone is a Selective 5-HT1A Receptor Agonist for Nervous System Disorders Research.

At first, Tandospirone (SM-3997) is a potent and selective 5-HT1A receptor partial agonist, with a Ki of 27 nM. Meanwhile, Tandospirone has anxiolytic and antidepressant activities. Nonetheless, Tandospirone can be used for the research of the central nervous system disorders and the underlying mechanisms.

Secondly, Tandospirone is approximately two to three orders of magnitude less potent at 5-HT2, 5-HT1C, α1-adrenergic, α2-adrenergic and dopamine D1 and D2 receptors than 5-HT1A. Tandospirone activates postsynaptic 5-HT1A receptor coupled with G-protein (Gi/o), resulting in inhibition of protein kinase A (PKA)-mediated protein phosphorylation and neuronal activity.

Thirdly, Tandospirone inhibits freezing behavior in the conditioned fear stress-induced freezing behavior rat model. Moreover, Tandospirone exhibits the anxiolytic effect dependent on the plasma concentration of at 0.5 hours but not 4 hours.

Finally, Tandospirone is a potent and selective 5-HT1A receptor partial agonist.

References:

[1] Hamik A, et al. Biol Psychiatry.1990 Jul 15;28(2):99-109.

[2] Kyoko Nishitsuji, et al. Eur Neuropsychopharmacol. 2006 Jul;16(5):376-82.