Neuronal Nicotinic Receptors - September 2008
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Neuronal nicotinic receptor ligands are fast proceeding through clinical development as exciting candidates for multiple CNS disorders including Alzheimer's disease; Schizophrenia; ADHD; Depression; Pain and Addiction.
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Table of Contents
What's in the September 2008 edition of UpdatesPlus-Nicotinic Receptors?
- Modification to the R3487/MEM 3454 program: Memory Pharmaceuticals has announced modifications to the Phase 2 program that it is co-developing with Roche to determine the effect of R3487/MEM 3454 on CIAS. At the same time, Memory has announced that Roche will be opening a Phase 2 trial to evaluate R3487/MEM 3454 in Alzheimer's disease. On the down-side, major job cuts will be effected at Memory to allow an increased focus on clinical development. LeadDiscovery examines the implications of these events
- News on AZD0328: Despite having entered Phase 2 development in May, AstraZeneca has announced that a Phase 1 food interaction study of AZD0328 will be opening. Why?
- α7 receptor involvement in neurovascular components of Alzheimer's disease: An interesting study has been published demonstrating intense beta amyloid binding to the CNS vasculature of Alzheimer’s disease patients. Staining overlaps with α7 nicotinic receptor expression and appears related to vascular smooth muscle cell death. What is the therapeutic potential behind this study? LeadDiscovery explains.
- Pfizer presence at the ESC: Pfizer had a strong presence at the 2008 European Society of Cardiology meeting. This is not surprising given the company’s market involvement in dyslipidemia and hypertension. The conference messaging also included a strong emphasis on smoking cessation centering around Chantix. See this messaging in UpdatesPlus.
- Pfizer investigation into the potential neuropsychiatric activity of Champix/Chantix: The sales of Champix have suffered from the introduction of a warning of neuropsychiatric symptoms on the Chantix product label. The possibility that withdrawal symptoms rather than Chantix/Champix contribute to neuropsychiatric symptoms is now being evaluated in a study being opened by Pfizer. Read about this study and why LeadDiscovery believes it will be challenging
- Development of a slow release formulation of varenicline: Pfizer is developing a slow release tablet formulation of varenicline, one aim of which is to reduce nausea. Pfizer has now advanced the slow release formulation into a large Phase 2 smoking cessation efficacy study.
- Is Pfizer developing a FDC varenicline/bupropion formulation: Prior to the approval of Chantix/Champix, Zyban (bupropion SR) was the dominant prescription smoking cessation product on the market. Pivotal studies demonstrated improved abstinence with varenicline compared to bupropion SR and this led to the approval of Chantix/Champix and subsequent erosion of bupropion SR sales. Pfizer is now sponsoring an investigator led study comparing the efficacy of Chantix/Champix plus bupropion SR versus the two products alone.
- Development of varenicline for the treatment of psychiatric disease: Pfizer has also taken the major step of opening Phase 2 studies to evaluate the efficacy of varenicline in psychiatric disease. Which indications are being investigated? What are the benefits and risks of Pfizer's approach
- Breaking data from SIROCCO: AstraZeneca/Targacept have announced that SIROCCO, a Phase 2 trial of AZD3480 in Alzheimer’s disease failed to meet its primary end-point. Read more about this key trial here
- Amgen enters the nicotinics field: Amgen has stepped into the pain arena and an α7 agonist with analgesic activity has recently been described. A series of potent and CNS selective α4β2 receptor modulators has now been reported.
- Full and up to date pipeline
UpdatesPlus continuously tracks development activity behind all known nicotinic agonists, antagonists and modulators including: MEM 63908/R4996, ABT-107, TC-5619, EVP-6124, AZD-0328, SSR-180711, GTS-21,MEM 3454 (R3487), Varenicline (Chantix/Champix), TC-6499, ABT-560, AZD3480 (TC-1734), TC-5214, Ispronicline, ABT-894, ABT-089
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