Vabicaserin (PF-05208769) / Pfizer - LARVOL DELTA

Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments. (PubMed, Pharmacopsychiatry) - "Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

The enhancing effect of 5-HT on phasic contractions of human isolated distal ureter and the mechanisms mediating these effects. (PubMed, Eur J Pharmacol) - "5-HT receptor selective agonist, vabicaserin, increased contraction frequency with an Emax of 35% of 5-HT...Blockade of voltage-gated sodium channels, α1-adrenergic receptors, adrenergic neurotransmission, and neurokinin-2 receptors using tetrodotoxin, tamsulosin, guanethidine, and Men10376, respectively, and desensitization of sensory afferents using capsaicin (100 μM), significantly reduced 5-HT effects...Sympathetic nerve and sensory afferents partly contributed to 5-HT effects. 5-HT and 5-HT receptors could be promising targets for ureteral stone expulsion."

Journal • Renal Calculi

Homology Modeling, de Novo Design of Ligands, and Molecular Docking Identify Potential Inhibitors of Leishmania donovani 24-Sterol Methyltransferase. (PubMed, Front Cell Infect Microbiol) - "The ligand A1 was predicted to possess antileishmanial properties with a probability of activity (Pa) of 0.362 and a probability of inactivity (Pi) of 0.066, while A5 and A6 possessed dermatological properties with Pa values of 0.205 and 0.249 and Pi values of 0.162 and 0.120, respectively. Structural similarity search via DrugBank identified vabicaserin, daledalin, zanapezil, imipramine, and cefradine with antileishmanial properties suggesting that the de-novo compounds could be explored as potential antileishmanial agents."

Journal • Dermatology • Infectious Disease

New Pharmacological Targets for the Treatment of Schizophrenia: A Literature Review. (PubMed, Curr Top Med Chem) - "This narrative report suggests a promising role of new agents in the treatment of Schizophrenia, even if more research is needed to approve their clinical employment."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Discovery of a lead series of potent benzodiazepine 5-HT receptor agonists with high selectivity in functional and binding assays. (PubMed, Bioorg Med Chem Lett) - "A series of potential new 5-HT receptor scaffolds based on a simplification of the clinically studied, 5-HTR agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. A subsequent early SAR investigation provided potent agonists of the 5-HT receptor that were highly selective in both functional and binding assays, had good rat PK properties and that significantly reduced acute food intake in the rat."

Journal

Serpentine and AJC-61 effects on cognitive deficit, locomotor activity and social interaction in phencyclidine (PCP)-treated mice and other behaviors are blocked by the 5-HT2C receptor antagonist, SB242084 (Neuroscience 2019) - "...The 5-HT2C agonist, vabicaserin, WAY 163909, was effective in preclinical models of antipsychotic activity and in treating acutely psychotic schizophrenia patients...AJC-61 or other compounds in this series are being investigated for several clinical indications, including schizophrenia. Supported by donations from the Weisman and Price families and a grant from the Center for Life Processes, Northwestern University."

Preclinical

Enzymatic late-stage oxidation of lead compounds with solubilizing biomimetic docking/protecting groups (ACS-Sp 2019) - "Vabicaserin was used as tool compound containing typical groups such as basic, aliphatic and aromatic moieties. The results were rationalized with the help of in silico docking and molecular dynamic studies (Chemistry – A European Journal in press)."