ABT-418

ABT-418 is a drug developed by Abbott, that has nootropic, neuroprotective and anxiolytic effects,^{[1][2][3][4][5]} and has been researched for treatment of both Alzheimer's disease^[6] and ADHD.^[7][8][9] It acts as an agonist at neural nicotinic acetylcholine receptors, subtype-selective binding with high affinity to the α₄β₂, α₇/5-HT₃, and α₂β₂ nicotinic acetylcholine receptors but not α3β4 receptors^[10][11][12] ABT-418 was reasonably effective for both applications and fairly well tolerated, but produced some side effects, principally nausea, and it is unclear whether ABT-418 itself will proceed to clinical development or if another similar drug will be used instead.^[13]

ABT-418

Identifiers
IUPAC name 3-Methyl-5-[(2S)-1-methylpyrrolidin-2-yl]-1,2-oxazole
CAS Number	147402-53-7 N
PubChem CID	119380
ChemSpider	106627 Y
UNII	B9I6MZL7BW
ChEMBL	ChEMBL274525 Y
CompTox Dashboard (EPA)	DTXSID10163711
Chemical and physical data
Formula	C9H14N2O
Molar mass	166.224 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=NOC(=C1)[C@@H]2CCCN2C
InChI InChI=1S/C9H14N2O/c1-7-6-9(12-10-7)8-4-3-5-11(8)2/h6,8H,3-5H2,1-2H3/t8-/m0/s1 Y Key:ILLGYRJAYAAAEW-QMMMGPOBSA-N Y
NY (what is this?)  (verify)

See also

• Epiboxidine
• Anabaseine

References

1. Arneric SP, Sullivan JP, Briggs CA, Donnelly-Roberts D, Anderson DJ, Raszkiewicz JL, et al. (July 1994). "(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization". The Journal of Pharmacology and Experimental Therapeutics. 270 (1): 310–318. PMID 7518514.
2. Decker MW, Brioni JD, Sullivan JP, Buckley MJ, Radek RJ, Raszkiewicz JL, et al. (July 1994). "(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: II. In vivo characterization". The Journal of Pharmacology and Experimental Therapeutics. 270 (1): 319–328. PMID 7913497.
3. Brioni JD, O'Neill AB, Kim DJ, Buckley MJ, Decker MW, Arneric SP (October 1994). "Anxiolytic-like effects of the novel cholinergic channel activator ABT-418". The Journal of Pharmacology and Experimental Therapeutics. 271 (1): 353–361. PMID 7965735.
4. Prendergast MA, Terry AV, Jackson WJ, Marsh KC, Decker MW, Arneric SP, Buccafusco JJ (April 1997). "Improvement in accuracy of delayed recall in aged and non-aged, mature monkeys after intramuscular or transdermal administration of the CNS nicotinic receptor agonist ABT-418". Psychopharmacology. 130 (3): 276–284. doi:10.1007/s002130050240. PMID 9151363. S2CID 34377165.
5. Dallanoce C, Magrone P, Matera C, Lo Presti L, De Amici M, Riganti L, et al. (December 2010). "Synthesis of novel chiral Δ2-isoxazoline derivatives related to ABT-418 and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes". European Journal of Medicinal Chemistry. 45 (12): 5594–5601. doi:10.1016/j.ejmech.2010.09.009. PMID 20932609.
6. Potter A, Corwin J, Lang J, Piasecki M, Lenox R, Newhouse PA (March 1999). "Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer's disease". Psychopharmacology. 142 (4): 334–342. doi:10.1007/s002130050897. PMID 10229057. S2CID 27337634.
7. Wilens TE, Biederman J, Spencer TJ, Bostic J, Prince J, Monuteaux MC, et al. (December 1999). "A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder". The American Journal of Psychiatry. 156 (12): 1931–1937. doi:10.1176/ajp.156.12.1931. PMID 10588407. S2CID 20375475.
8. Horrigan JP (April 2001). "Present and future pharmacotherapeutic options for adult attention deficit/hyperactivity disorder". Expert Opinion on Pharmacotherapy. 2 (4): 573–586. doi:10.1517/14656566.2.4.573. PMID 11336608. S2CID 41914443.
9. Spencer T, Biederman J (2002). "Non-stimulant treatment for Attention-Deficit/Hyperactivity Disorder". Journal of Attention Disorders. 6 (Suppl 1): S109–S119. doi:10.1177/070674370200601s13. PMID 12685525. S2CID 26801069.
10. Papke RL, Thinschmidt JS, Moulton BA, Meyer EM, Poirier A (February 1997). "Activation and inhibition of rat neuronal nicotinic receptors by ABT-418". British Journal of Pharmacology. 120 (3): 429–438. doi:10.1038/sj.bjp.0700930. PMC 1564486. PMID 9031746.
11. Dallanoce C, Magrone P, Matera C, Lo Presti L, De Amici M, Riganti L, et al. (December 2010). "Synthesis of novel chiral Δ2-isoxazoline derivatives related to ABT-418 and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes". European Journal of Medicinal Chemistry. 45 (12): 5594–5601. doi:10.1016/j.ejmech.2010.09.009. PMID 20932609.
12. Briggs CA, McKenna DG, Piattoni-Kaplan M (June 1995). "Human alpha 7 nicotinic acetylcholine receptor responses to novel ligands". Neuropharmacology. 34 (6): 583–590. doi:10.1016/0028-3908(95)00028-5. PMID 7566493. S2CID 54338489.
13. Wilens TE, Decker MW (October 2007). "Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition". Biochemical Pharmacology. 74 (8): 1212–1223. doi:10.1016/j.bcp.2007.07.002. PMC 2974320. PMID 17689498.