ACADIA Pharmaceuticals Inc.

About: ACADIA Pharmaceuticals Inc. is a company organization based out in San Diego, California, United States. It is known for research contribution in the topics: Pimavanserin & Receptor. The organization has 260 authors who have published 276 publications receiving 8418 citations.

A 3-way Cross-over Study of Pregabalin, Placebo, and the Histamine 3 Receptor Inverse Agonist AZD5213 in Combination With Pregabalin in Patients With Painful Diabetic Neuropathy and Good Pain-reporting Ability.

Abstract: OBJECTIVES In this study, patients with painful diabetic neuropathy were trained using an experimental pain paradigm in an attempt to enroll a subset of patients who are "pain connoisseurs" and therefore more able to discriminate between active and placebo treatments. METHODS AZD5213, a novel histamine H3 receptor inverse agonist+pregabalin, pregabalin, and placebo were then tested in a 3-period cross-over. RESULTS The study did not provide any evidence of clinical efficacy for AZD5213 when combined with pregabalin in the treatment of painful diabetic neuropathy. DISCUSSION The training of study patients in pain reporting and subsequent enrichment with good pain reporters also did not enable the robust detection of the efficacy of pregabalin relative to placebo in a small sample size. Further work is required before recommending the use of "connoisseur" patients in future neuropathic pain studies.

The A-CD analogue of 16 beta,17 alpha-estriol is a potent and highly selective estrogen receptor beta agonist

Abstract: Selective estrogen receptor β (ERβ) agonists display neuroprotective properties in animal models and hold promise in the treatment of neurodegenerative diseases. In our quest to design, synthesize and evaluate potent and safe ERβ agonists, we focused on making an analogue of 16β,17α-estriol (16,17-epiestriol), a potent and one of the most ERβ selective endogenous estrogens reported. Herein we disclose the synthesis and in vitro evaluation of an analogue based on the recently introduced A-CD scaffold. A 14-step synthesis based on the Hajos–Parrish ketone resulted in the discovery of (1S,2S,3aS,5S,7aS)-5-(4-hydroxyphenyl)-7a-methyloctahydro-1H-indene-1,2-diol (15). This A-CD analogue of 16β,17α-estriol is a highly selective (500-fold) ERβ full agonist over ERα with a pEC50 of 7.7 at ERβ. Molecular modelling suggests that 15 turns around in the ligand-binding domain compared to estriol, thus the 7a-methyl occupies the α-face, which might explain the high selectivity.

Chemical genomics: massively parallel technologies for rapid lead identification and target validation

Abstract: Chemical genomics is a new research paradigm with importantapplications in drug discovery It links genomic targets withsmall-molecule chemistries thereby allowing for efficient targetvalidation and lead compound identification ACADIA'schemical-genomics platform consists of a large and diverse small-moleculelibrary (800,000), a reference drug library (2,000), druggablegenomic targets (>300) and a cell-based functional assaytechnology (R-SATTM; Receptor Selection and AmplificationTechnology) that allows for ultra-high throughput screening(>500,000 data points/week) as well as high throughputpharmacology and profiling over a wide range of targets Twoexamples are presented that illustrate the success of ourchemical-genomics approach: (i) The validation of inverse agonismat serotonin 5-HT2A receptors as an antipsychotic mechanismand the subsequent discovery of potent and selectively acting 5-HT2A inverse agonists, currently in preclinical development,and (ii) the discovery of the first ectopically binding subtype-selective muscarinic m1 agonist

5-ht2a serotonin receptor inverse agonists or antagonists for use in reducing amyloid-beta peptides and accumulation of amyloid plaques

Abstract: Described are compounds and compositions for use in methods for reducing the rate of accumulation of amyloid plaques in a subject by administering a 5-HT2A serotonin receptor inverse agonist or antagonist, or pharmaceutically acceptable salts thereof.