A-582941 was found to exhibit high-affinity binding and agonism at alpha-7 nicotinic acetylcholine receptor (α7-nAChR), with acceptable pharmacokinetic properties and excellent distribution to the central nervous system. In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation. A-582941 enhanced cognitive performance in behavioral assays including the monkey delayed matching-to-sample, rat social recognition, and mouse inhibitory avoidance models that capture domains of working memory, short-term recognition memory, and long-term memory consolidation, respectively. AbbVie is developing α7-nAChR agonists including A-582941 as neuroprotective agents for the treatment of cognitive disorders such as Alzheimer's disease and schizophrenia. Development is at the preclinical stage.

CHOLINE is a basic constituent of lecithin that is found in many plants and animal organs. Choline was officially recognized as an essential nutrient by the Institute of Medicine in 1998.1 Its role in the body is complex. It is needed for neurotransmitter synthesis (acetylcholine), cell-membrane signaling (phospholipids), lipid transport (lipoproteins), and methyl-group metabolism (homocysteine reduction). It is the major dietary source of methyl groups via the synthesis of S-adenosylmethionine (AdoMet). At least 50 AdoMet-dependent reactions have been identified in mammals, and it is likely that the number is much higher. Choline is required to make the phospholipids phosphatidylcholine, lysophosphatidylcholine, choline plasmalogen, and sphingomyelin—essential components for all membranes. It plays important roles in brain and memory development in the fetus and appears to decrease the risk of the development of neural tube defects. The importance of choline in the diet extends into adulthood and old age. In a study of healthy adult subjects deprived of dietary choline, 77% of the men and 80% of the postmenopausal women developed signs of subclinical organ dysfunction (fatty liver or muscle damage). Less than half of premenopausal women developed such signs. Ten percent of the subjects studied developed fatty liver, muscle damage, or both when they consumed the Adequate Intake (AI) of choline. The damage was reversed when they consumed a high-choline diet. Plasma choline concentration has been found to vary in response to diet, decreasing approximately 30 percent in humans fed a choline-deficient diet for 3 weeks. Based on estimated dietary intakes and studies reporting liver damage with lower choline intakes, the Institute of Medicine, Food and Nutrition Board set the AI for choline at 425 milligrams/per day for women aged 19 and older, and 550 milligrams/per day for men aged 19 and older.