Name: ABT 418
Chemical Name: 3-methyl-5-[(2S)-1-methylpyrrolidin-2-yl]-1,2-oxazole
Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Approved for: None
Acute administration of nicotine to AD patients improved accuracy of delayed recall, as well as deficits in attention and information processing (Sahakian et al. 1989; Wesnes and Warburton, 1984; Jones et al, 1992). However, nictoine has significant side effects including tachycardia, elevated blood pressure, and gastrointestinal distress. Agonists with better selectivity for nAChR subtypes that mediate the beneficial effects could be useful. ABT-418 is a novel bioisostere of (-)-nicotine. Like nicotine, it is an agonist for nicotinic acetylcholine receptors (nAChRs), ionotropic receptors composed of five subunits arranged around a central pore. It is unclear which nicotinic receptor subtypes are preferentially activated by ABT-418.
- Sahakian B, Jones G, Levy R, Gray J, Warburton D. The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry. 1989 Jun;154:797-800. PubMed.
- Wesnes K, Warburton DM. Effects of scopolamine and nicotine on human rapid information processing performance. Psychopharmacology (Berl). 1984;82(3):147-50. PubMed.
- Jones GM, Sahakian BJ, Levy R, Warburton DM, Gray JA. Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease. Psychopharmacology (Berl). 1992;108(4):485-94. PubMed.
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