Loading…
for educational and safety purposes
Zuranolone and Aticaprant both come up in the same conversations. Zuranolone: Zuranolone (development code SAGE-217; marketed as Zurzuvae) is an orally bioavailable synthetic analog of allopregnanolone (a naturally occurring neurosteroid derived from progesterone) that acts as a positive allosteric modulator (a compound that amplifies a receptor's response to its own transmitter) of the GABA-A receptor (the brain's principal inhibitory chloride channel). Aticaprant: Aticaprant is a selective kappa-opioid receptor (KOR) antagonist that has traveled under several names over the years: JNJ-67953964, CERC-501, LY2456302, and the older nickname Opra Kappa.
Zuranolone (development code SAGE-217; marketed as Zurzuvae) is an orally bioavailable synthetic analog of allopregnanolone (a naturally occurring neurosteroid derived from progesterone) that acts as a positive allosteric modulator (a compound that amplifies a receptor's response to its own transmitter) of the GABA-A receptor (the brain's principal inhibitory chloride channel). It was engineered by Sage Therapeutics from the same neurosteroid scaffold as the intravenous agent brexanolone, but with a modified 3-hydroxy pyrazole substitution that confers metabolic stability suitable for once-daily oral tablets rather than a continuous infusion. In August 2023 the United States Food and Drug Administration approved zuranolone for postpartum depression (a major depressive episode arising in the weeks after childbirth), making it the first oral drug indicated specifically for that condition. It is notable for producing an antidepressant response within days when given as a short, fixed two-week course, in contrast with the weeks-long onset of conventional monoamine antidepressants.
Aticaprant is a selective kappa-opioid receptor (KOR) antagonist that has traveled under several names over the years: JNJ-67953964, CERC-501, LY2456302, and the older nickname Opra Kappa. The idea behind it is elegant; the brain's dynorphin/KOR system acts as an 'anti-reward' brake that stress ramps up, dampening dopamine and blunting pleasure, so blocking KOR should ease anhedonia and low mood. It reached clinical-stage development for major depressive disorder, mostly as an add-on to standard SSRIs/SNRIs and aimed at people with prominent anhedonia, and along the way it was also explored in substance-use and anxiety contexts. Early-phase results were promising and it is generally well tolerated, but the effect sizes have been small, and the late-stage program has been underwhelming; the pivotal phase 3 depression trials were discontinued after they did not clearly beat placebo. In short, a mechanistically novel, well-tolerated drug whose real-world antidepressant punch has so far looked modest.
both fingerprints on one instrument; where the marks line up the two compounds work the same lever, where a slot goes dark only one of them touches it. read straight from each entry's affinity table; nothing here is invented.
Positive allosteric modulation and direct gating at higher concentrations, enhancing tonic inhibitory current
positive allosteric modulator of phasic inhibition
Selective agonist binding distinct from the benzodiazepine site
Positive allosteric modulation of GABA-evoked phasic currents
Concentration-dependent potentiation across alpha and beta subunit combinations
blocks
selective antagonist
disinhibits (indirect)
weak antagonist (~30x less than KOR)
strengths are the entries' qualitative ratings (strong / moderate / weak); Ki and EC50 figures appear where an entry records them.