PH-670187 (Deramciclane; EGIS-3886)

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Pfizer Inc. PH-670187 (deramciclane; EGIS-3886) 5-Hydroxytryptamine 2A/2C receptor (5-HT2A/2C) antagonist Mechanism of Action http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=6 http://www.ncbi.nlm.nih.gov/gene/3356 ; http://www.ncbi.nlm.nih.gov/gene/3358 Deramciclane is a relatively selective functional antagonist of 5-HT2C and 5-HT2A, that potentially also acts as a 5-HT2B Overview antagonist based on similar potency in in vitro experiments. Although feasible, weak effects on dopaminergic (antagonist), κ- opiate (agonist), and σ1 receptors are improbable in vivo. Deramciclane has been safe and well tolerated up to 150 mg in all clinical studies. In Phase 2 – 3 studies, there were no clinically significant differences in the incidence of adverse events (AEs), laboratory variables, vital signs, and ECG between Safety/Tolerability the deramciclane groups and placebo. No evidence for sedative effects or worsening of psychomotor performance was observed. In addition, no withdrawal reactions have been seen. PET ligand data demonstrated maximal brain 5-HT2A receptor occupancy at plasma concentrations of 70 ng/ml (~60 mg dose) in humans. Due to its unique mechanism of action, deramciclane seems to be well tolerated and without typical adverse Additional Information reactions of other anxiolytics, such as sedative or muscle relaxant effects, abuse potential, withdrawal reactions, initial drug- induced increase in agitation or anxiety, weight change, cognitive impairment, and sexual adverse reactions. Suitable for and Exclusions Efficacy/differentiation in Phase 3 for Generalized Anxiety Disorder (GAD) was insufficient to advance further. Clinical Trials http://www.ncbi.nlm.nih.gov/pubmed?term=deramiciclane%20and%20clinical%20trial http://www.ncbi.nlm.nih.gov/pubmed?term=deramciclane http://www.ncbi.nlm.nih.gov/pubmed/15949921 Publications http://www.ncbi.nlm.nih.gov/pubmed/10445375 http://www.ncbi.nlm.nih.gov/pubmed/9551765 .

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