MK-8435 / Merck (MSD) - LARVOL DELTA

Determination of glycine transporter 1 levels with [3H]-NFPS binding in hemi-parkinsonian rats with L-DOPA induced dyskinesia (MDS Congress 2022) - "After brain sectioning, we measured GlyT1 levels in the striatum, globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra pars reticulata and pars compacta, the motor thalamus, as well as the primary motor cortex, by performing autoradiographic binding using [3H]-NFPS in the presence of ORG-25935 as the cold ligand... Our findings indicate that GlyT1 inhibition may act in the globus pallidus and the thalamus to diminish dyskinesia in PD. On the other hand, administration of L-DOPA appears to be associated with increased GlyT1 levels in the subthalamic nucleus. Further studies are warranted to shed light on the mechanisms and circuitry underlying GlyT1 involvement in PD and dyskinesia."

Preclinical • CNS Disorders • Parkinson's Disease

Pilot Study of ORG 25935 Modulation of Ketamine-induced Behavioral and Cognitive Effects in Healthy Male Subjects (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Yale University | Active, not recruiting ➔ Completed

Trial completion • BDNF

Pilot Study of ORG 25935 Modulation of Ketamine-induced Behavioral and Cognitive Effects in Healthy Male Subjects (clinicaltrials.gov) - P1; N=18; Active, not recruiting; Sponsor: Yale University; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Jun 2021

Clinical • Trial completion date • Trial primary completion date • BDNF

Recent development of piperazine and piperidine derivatives as antipsychotic agents. (PubMed, Mini Rev Med Chem) - "In this direction various antipsychotic drugs have been synthesized at laboratory level and few are under clinical trial studies such as Lu AE58054, PF-04802540, ORG25935, DMXB-A, Bitopertin and ABT-126. In the present review, we include the studies related to the effect of different substituents on piperidine/piperazine derivatives and their anti-psychotic activity. Various series of synthesized compounds by different researchers with piperidine/piperazine nucleus have been reviewed and diagrammatically represented in the form of SAR (structure activity relationships) which will help to the scientists for the development of potential lead compounds."

Journal • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

Glycine transporter inhibitors: a new avenue for managing neuropathic pain. (PubMed, Brain Res Bull) - "This pathological overactivation of NR1/NR2B receptors can be reduced by GlyT-1 inhibitors (NFPS, Org-25935), which decrease excessive glycine release from astroglial cells or by selective antagonists of NR2B subunits (ifenprodil, Ro 25-6981). In addition, the possible mechanisms of action of the GlyT inhibitors, i.e. how they affect the neurochemical and pain transmission in the spinal cord, are also discussed. The growing evidence for the possible therapeutic intervention of neuropathic pain by GlyT inhibitors further urges development of drugable compounds, which may beneficially restore impaired pain transmission in various neuropathic conditions."

Journal • Review • Immunology • Neuralgia • Pain

Pilot Study of ORG 25935 Modulation of Ketamine-induced Behavioral and Cognitive Effects in Healthy Male Subjects (clinicaltrials.gov) - P1; N=18; Active, not recruiting; Sponsor: Yale University; Trial completion date: Jun 2020 ➔ Dec 2020; Trial primary completion date: Jun 2020 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date • BDNF

Pilot Study of ORG 25935 Modulation of Ketamine-induced Behavioral and Cognitive Effects in Healthy Male Subjects (clinicaltrials.gov) - P1; N=18; Active, not recruiting; Sponsor: Yale University; Trial completion date: Dec 2019 ➔ Jun 2020; Trial primary completion date: Dec 2019 ➔ Jun 2020

Clinical • Trial completion date • Trial primary completion date • BDNF