Zuranolone (ZURZUVAE™) is an oral positive allosteric modulator of CNS GABA signaling developed by Sage Therapeutics, in collaboration with Biogen, which was approved in August 2023 by the FDA for the treatment of postpartum depression (PPD). In 2019 Sage had received approval for brexanolone (ZULRESSO™), an IV formulation of the endogenous GABA PAM neurosteroid hormone for PPD, but an oral drug is expected to greatly increase access to treatment. Zuranolone was also investigated for major depressive disorder, although the FDA declined to extend approval for this indication.

The Takeda GPR139 agonist, TAK-041 , is a CNS-penetrant GPCR agonist being explored for schizophrenia symptoms and is an interesting example of a triazinone-containing clinical candidate. GPR139 is an orphan GPCR that’s highly expressed in the human habenula, which plays a major role in avoidance behavior. Lesions in the habenula cause [...]

KLS-13019 is a CBD (cannabidiol) analogue and GPR55 (G protein-coupled receptor 55) antagonist from Kannalife Sciences, which shows promise as a novel therapeutic for neuropathic pain, particularly chemotherapy-induced neuropathic pain.

The Altos Therapeutics /Takeda D2/D3 receptor antagonist, TAK-906 , is a peripherally-restricted, non-BBB penetrant molecule, targeting the stomach and vomiting center in the area postrema to treat gastroparesis. Gastroparesis is a chronic condition characterized by delayed gastric emptying, resulting in nausea, vomiting, pain, and anorexia [...]

Compound 8 is a dual 5-HT2A and 5-HT2C receptor inverse agonist developed to address the limitations of pimavanserin.