Esketamine is an S(+)-enantiomer of ketamine. It is a nonselective, noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptor. A nasal spray, containing esketamine, was approved in 2019 for the treatment of treatment-resistant depression in adults, in conjunction with an oral antidepressant, and is marketed under tradename SPARAVATO. Esketamine is a schedule III drug product in the USA.

JNJ-40411813 (aka ADX71149) is a metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator (PAM) that has the potential to be the first oral non-dopaminergic drug that may address both the positive and negative symptoms of schizophrenia and other indications, such as anxiety. ADX71149 is differentiated from marketed antipsychotics in that it may also show efficacy on negative symptoms and avoid compliance-limiting side effects such as weight gain, hyperprolactinemia and extrapyramidal symptoms, which are associated with the use of dopamine antagonists. The development of ADX71149 is part of a worldwide research collaboration and license agreement between Addex and Janssen Pharmaceuticals, Inc. This drug was also investigated for use as an adjunctive treatment for major depressive disorder (MDD), however, these studies were discontinued. JNJ-40411813 is now in phase II clinical trial for the treatment of epilepsy.