evt 101

EVT-101, also known as ENS-101, is an experimental medication which originated from Roche and is under development by Evotec AG for the treatment of major depressive disorder. It acts as a selective NMDA receptor subunit 2B (NR2B) antagonist.

Phenylbutazone-d9 is intended for use as an internal standard for the quantification of phenylbutazone by GC- or LC-MS. Phenylbutazone is a non-steroidal anti-inflammatory drug and an inhibitor of the peroxidase activity of COX (IC50 = ~100 µM in the presence of hydrogen peroxide). It also inhibits prostaglandin I synthase (IC50 = ~25 µM in the presence of hydrogen peroxide). Phenylbutazone (2 mg kg) reduces increases in type II collagen levels in the inflamed joints of an equine model of LPS-induced acute synovitis. Formulations containing phenylbutazone have been used in the treatment of lameness in horses.

EVT-101 is a GluN2B antagonist, binding at the same GluN1 GluN2B dimer interface as ifenprodil but adopting a remarkably different binding mode involving a distinct subcavity and receptor interactions.

Ro 04-5595 is a selective antagonist of NMDA receptors NR2B subunits. Ro 04-5595 had an EC 50 of 186 ± 32 nmol L. Ro 04-5595 was predicted to bind the EVT-101 binding site, not the ifenprodil-binding site. Specific binding, defined with a new NR2B-specific antagonist Ro 04-5595 at 10 microM was fully inhibited by several compounds with the following rank order of affinities--Ro 25-6981 > CP-101,606 > Ro 04-5595 = ifenprodil >> eliprodil > haloperidol > spermine > spermidine > MgCl2 > CaCl2--and partially inhibited by competitive glutamate recognition site antagonists. Complementary high-resolution autoradiographic images using [3H]Ro04-5595 demonstrated strong binding in NR2B receptor-rich regions and low binding in cerebellum where NR2B concentration is low.