DU125530 is a Potent and Selective 5-HT1A Receptor Antagonist and has Antidepressant Effects

5-HT1A receptor is a subtype of 5-HT receptors that bind 5-HT. It is a G protein-coupled receptor that can couple to Gi proteins. In the brain, 5-HT1A activation mediates hyperpolarization and a decrease in the firing rate of postsynaptic neurons. 5-HT1A receptors are the most widely distributed of all 5-HT receptors. Generally, they are present in the cerebral cortex, hippocampus, septum, amygdala, and raphe nucleus. Only a small amount of 5-HT1A receptors are in the basal ganglia and thalamus. Furthermore, 5-HT1A receptors play an important role in neuromodulation. They can reduce blood pressure and heart rate by inducing peripheral vasodilation and stimulating the vagus nerve.

Activation of 5-HT1A receptors also can increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus. Besides, it may help improve symptoms of schizophrenia and Parkinson’s disease. In addition, activation of 5-HT1A receptors can also impair certain aspects of memory and learning by inhibiting the release of glutamate and acetylcholine in various regions of the brain. Moreover, the use of 5-HT1A antagonists can alleviate the learning and memory impairment caused by glutamate blockade. For example, DU125530 is an effective and selective 5-HT1A receptor antagonist and has potential antidepressant effects.

DU125530 is a potent and selective 5-HT1A receptor antagonist.

DU125530 is a potent and selective 5-HT1A receptor antagonist with Ki values of 0.7, 890, 1200, 240, 750, and 1100 nM for 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, 5-HT3, respectively. In some in vivo studies, DU125530 (3 mg/kg; s.c.) can prevent the reduction of 5-HT release induced by 8-OH-DPAT in WT mice, alone has no effect on the extracellular 5-HT concentration in mPFC of wild-type mice (WT) nor in 5-HT1A receptor knock-out mice (KO).

In conclusion, DU125530 is a potent and selective 5-HT1A receptor antagonist with antidepressant effects.


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[2] M C Scorza1, et al. Br J Pharmacol. 2012 Nov;167(5):1021-34.