AZD1466 / AstraZeneca, Gyre Therapeutics - LARVOL DELTA

Nicotine-mediated effects in neuronal and mouse models of synucleinopathy. (PubMed, Front Neurosci) - "Moreover, when investigating the role of nicotinic acetylcholine receptor (nAChR) signaling in nicotine's neuroprotective effects in iPSC-derived dopaminergic neurons, we observed that while α4-specific antagonists reduced the nicotine-induced calcium response, α4 agonists (e.g., AZD1446 and anatabine) mediated similar neuroprotective responses against α-Syn PFF-provoked neurodegeneration. Our results show that nicotine attenuates α-Syn-provoked neuropathology in vivo and in a humanized neuronal model of synucleinopathy and that activation of α4β2 nicotinic receptors might mediate these neuroprotective effects."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease

Evidence for alpha nicotinic receptor activation during the cough suppressing effects induced by nicotine and identification of ATA-101 as a potential novel therapy for the treatment of chronic cough. (PubMed, J Pharmacol Exp Ther) - "We additionally observed that the αβ-selective agonist Tc-6683 was without effect on evoked cough responses in guinea pigs, while the α-selective agonist PHA 543613 dose-dependently inhibited evoked coughing. Significance Statement This study documents the antitussive actions of nicotine and identifies the α nicotinic receptor subtype as the target for nicotine during cough suppression described in humans. We additionally present evidence suggesting that ATA-101 and other α nicotinic receptor selective agonists may be promising candidates for the treatment of chronic refractory cough."

Journal • Chronic Cough • CNS Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases

AZD1446 (TC-6683), a novel alpha4beta2 nAChR agonist with cognitive-enhancing properties (Neuroscience 2012) - Presentation time: Tuesday, Oct 16, 2012, 10:00 AM -11:00 AM; AZD1446 reverseed cognitive deficits produced by scopolamine and dizocilpine in RAM and WM models and improves attentional performance in normal animals and reverses impairments (10mg/kg) in dizoclipine-treated animals; Cognitive enhancing properties are long-lasting (18h in NOR and 24h in RAM) and sustained following repeated dosing

Preclinical-animal • Alzheimer's Disease

Researchers funded by the DMRF evaluate AZD1446as a possible dystonia drug [Google translation] - "Dystonia Cure have now jointly supported a research survey to explore whether a drug called AZD1446 that could potentially provide relief for patients with dystonia with fewer side effects than existing medications....The research was led by David Standaert."

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Targacept lays off 46 percent of its workforce (Journalnow) - The next research updates for Targacept are expected in Q2-Q4 2012 for a P2 trial for the AZD1446 compound for Alzheimer's disease; Results from P2 trials of TC-5619 for attention-deficit hyperactivity disorder and schizophrenia are expected in H2 2012 and mid-2013, respectively

Anticipated P2 data • Alzheimer's Disease • Schizophrenia

Development pipeline update (AstraZeneca Press Release) - AZD1446 discontinued for Alzheimer’s disease due to safety / efficacy reasons. AZD3480 discontinued for Alzheimer’s disease due to safety / efficacy reasons.

Discontinued • Alzheimer's Disease

Cingulate impairments in ADHD: Comorbidities, connections, and treatment. (PubMed, Handb Clin Neurol) - "Methylphenidate decreases hyperactivity in aMCC...AZD1446 (ɑ4β2 nAChR agonist) improves the Groton Maze task due to high nAChR in dPCC/RSC engaged in spatial orientation...Thus, ADHD children/adolescents respond impulsively to the significance of stimuli without having cortical inhibition. Finally, controls show negative relationships between aMCC and the default mode network, and ADHD compromises this relationship, showing decreased connectivity between ACC and precuneus/PCC."

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