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.

Pimavanserin Promotes Trophic Factor Release and Protects Cultured Primary Dopaminergic Neurons Exposed to MPP+ in a GDNF-Dependent Manner.

Abstract: Neurodegeneration and impaired neural development are a common feature of many neuropsychiatric disorders. Second-generation antipsychotics (SGAs) and certain atypical antidepressants display neuroprotective effects. Though these drugs interact with many molecular targets, a common shared attribute is high antagonist potency at 5-HT2A receptors. Pimavanserin is a selective 5-HT2A inverse agonist/antagonist that was recently FDA approved for treating hallucinations and delusions associated with Parkinson's disease. Unlike SGAs, pimavanserin lacks activity at other targets like dopamine, histamine, muscarinic, and adrenergic receptors. To investigate whether selective 5-HT2A inverse agonists have neuroprotective properties, pimavanserin and another selective 5-HT2A inverse agonist, M100907, were applied to primary cultures of dopaminergic neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Both pimavanserin and M100907 protected dopaminergic neurons against MPP+-induced cell death. The neuroprotective effects of pimavanserin required signaling through the extracellular signal-regulated kinase 1/2 pathway, restored mitochondrial function, and reduced oxidative stress. Further investigation showed that pimavanserin promotes the release of brain-derived neurotrophic factor and glial-derived neurotrophic factor (GDNF) and that the neuroprotective effects of pimavanserin were blocked by antibodies to GDNF but not by anti-tyrosine receptor kinase B receptor antibodies. Thus, pimavanserin induces release of neurotrophic factors and protects dopaminergic neurons against MPP+ toxicity in a GDNF-dependent manner.

High troughput functional assay for g-protein coupled receptors using a rap-ras chimeric protein

Abstract: Disclosed herein are methods for enabling or improving functional assays of G-protein coupled receptors through the use of co-expression of helper genes. In some cases, chimeras linking the regulatory domain of the rap1B protein to the effector region of the ras oncogene are used in conjuction with existing functional assays for cellular proliferation. Furthermore, overexpression of other genes can further augment the enabling properties of ras/rap chimeras.

Crystalline form of n-(4-fluorobenzyl)-n-(1-methylpiperidin-4-yl)-n'-(4-(2-methylpropyloxy)phenylmethyl)carbamide hemi-tartrate

Abstract: A crystalline form of N- (4-fluorobenzyl) -N- (1-methylpiperidin-4-yl) -N '- (4- (2-methylpropyloxy) phenylmethyl) carbamide hemitertrate of formula IV, ** Formula ** which (a) shows an X-ray powder diffraction pattern comprising peaks that have d-enangstroms values of about 12.0, about 10.7, about 5.86, about 4.84, about 4, 70, about 4.57, and about 3.77; or (b) shows an endothermic signal near 177 ° C with a fusion enthalpy of about 129 J / g, as determined by differential scanning calorimetry.

Synthesis of 2‐Substituted Pyridines via a Regiospecific Alkylation, Alkynylation, and Arylation of Pyridine N‐Oxides.

Abstract: [structure: see text]. Sequential addition of Grignard reagents to pyridine N-oxides in THF at room temperature followed by treatment with acetic anhydride at 120 degrees C afforded 2-substituted pyridines in good to high yields. Furthermore, by exchanging acetic anhydride for DMF in the second step, 2-substituted pyridine N-oxides were obtained, as intermediates suitable for addition of a second Grignard reagent for the synthesis of 2,6-disubstituted pyridines.

A patient journey analysis: Identification and treatment of dementia with Lewy bodies: Developing topics

Abstract: Between 3.2%‐7.1% of dementia patients are diagnosed with DLB. There is limited research on the identification and treatment of DLB, indicating an unmet need for this condition.[2] [1] Hogan D, Fiest K, Roberts J, Maxwell C, Dykeman J, Pringsheim T, Jetté N. (2016). The Prevalence and Incidence of Dementia with Lewy Bodies: A Systematic Review. Canadian Journal of Neurological Sciences / Journal Canadien Des Sciences Neurologiques, 43(S1), S83‐S95. doi:10.1017/cjn.2016.2. [2] Monfared A, Meier G, Perry R, Joe D. Burden of disease and current management of Dementia with Lewy Bodies: a literature review. Neurol Ther, 2019, 8:289‐305.