Nelotanserin

Nelotanserin (APD125) is a small molecule compound, a potent full inverse agonist of 5-HT2A (IC50=1.7 nM), a moderately potent partial inverse agonist of 5-HT2C (IC50=79 nM), and a weak inverse agonist of 5-HT2B (IC50=791 nM), with high selectivity and favorable pharmacological properties for research related to psychiatric disorders.

5-HT2C receptor:79 nM, 5-HT2B receptor:791 nM, 5-HT2A receptor:1.7 nM

Methods: The functional activity of Nelotanserin on 5-HT2A, 5-HT2C, and 5-HT2B receptors was assessed by IP accumulation assays, and its affinity for recombinant human 5-HT2A, 5-HT2C, and 5-HT2B receptors was determined by radioligand binding assays.
Results: Nelotanserin is a potent 5-HT2A full inverse agonist (IC50=1.7 nM), a moderately potent 5-HT2C partial inverse agonist (IC50=79 nM, with maximal response at 62% of clozapine), and a weak 5-HT2B inverse agonist (IC50=791 nM); it exhibits the highest affinity for 5-HT2A receptors (Ki=0.35 nM), moderate affinity for 5-HT2C receptors (Ki=100 nM), and low affinity for 5-HT2B receptors (Ki=2000 nM), with 262-fold higher affinity for 5-HT2A than 5-HT2C and 6610-fold higher affinity for 5-HT2A than 5-HT2B.[1]

Methods: In an MPTP-lesioned marmoset model, Nelotanserin (0.1, 0.3, 1 mg/kg) was administered by single subcutaneous injection concurrent with L-DOPA dosing, dissolved in 10% DMSO/saline; the control group received an equal volume of solvent, with observation for 6 hours.
Results: Nelotanserin at 0.3 and 1 mg/kg reduced peak-dose dyskinesia by 47% and 69%, respectively, and overall dyskinesia by 40% and 55%, respectively, without affecting the anti-Parkinsonian effect of L-DOPA.[2]
Methods: In an MPTP-lesioned marmoset model, Nelotanserin (0.1, 0.3, 1 mg/kg) was combined with L-DOPA and administered by single subcutaneous injection, dissolved in 10% DMSO/saline; the control group received an equal volume of solvent, with observation for 6 hours.
Results: Nelotanserin at 0.3 and 1 mg/kg reduced peak-dose dyskinesia by 47% and 69%, respectively, and overall dyskinesia by 40% and 55%, respectively, without affecting the anti-Parkinsonian effect of L-DOPA.[3]

DMSO: 250 mg/mL (571.77 mM), Sonication is recommended.