Serodolin | ß-Arrestin-biased 5-HT7 antagonist

Serodolin (1814929-81-1) is a potent dual antagonist of the serotonin receptors 5-HT₇ (Ki = 6.2 nM; IC₅₀ = 5.7 nM cAMP response) and 5-HT_2A (Ki = 19 nM; IC₅₀ = 110 nM IP1 response) with significant selectivity over 5-HT_1A and 5-HT₆.¹ Serodolin has recently been found to act as a ß-arrestin-biased inverse agonist on G_s signaling while inducing ERK activation requiring c-SRS activation, a unique pharmacological profile among 5-HT₇ ligands.²  It decreased hyperalgesia and pain sensation in response to inflammatory, thermal, and mechanical stimulation in a mouse model demonstrating the therapeutic potential of a ß-arrestin-biased ligand for pain relief.  Blood-brain barrier permeable.

References/Citations:

1. Deau et al. (2015), Rational Design, Pharmacomodulation, and Synthesis of Dual 5-Hydroxytryptamine 7 (5-HT₇)/5-Hydroxytryptamine 2A (5-HT_2A) Receptor Antagonists and Evaluation by [¹⁸F]-PET Imaging in a Primate Brain; J. Med. Chem. 58 8066
2. El Kamlichi et al. (2022), Serodolin, a ß-arrestin-biased ligand of 5-HT₇ receptor, attenuates pain-related behaviors; Proc. Natl. Acad. Sci. USA 119 e2118847119