ABT-089 [3-(2(S)-pyrrolidinylmethoxy)-2-methylpyridine]: An orally effective cholinergic channel modulator with potential once-a-day dosing and cardiovascular safety

Drug Development Research

Volumn 41, Issue 1, 1997, Pages 31-43

  Arneric, Stephen P ^a   Campbell, Jeffrey E ^a   Carroll, Sherry ^a   Daanen, Jerome F ^a   Holladay, Mark W ^a   Johnson, P ^a   Lin, Nan Horng ^a   Marsh, Kennan C ^a   Peterson, Bud ^a   Qui, Yihong ^a   Roberts, Ellen M ^a   Rodrigues, A David ^a   Sullivan, James P ^a   Trivedi, Jay ^a   Williams, Michael ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Acetylcholine; Cholinergic channel modulator; High performance liquid chromatography; Nicotine; Nicotinic acetylcholine receptor

Indexed keywords

2 METHYL 3 (2 PYRROLIDINYLMETHOXY)PYRIDINE; 3 METHYL 5 (1 METHYL 2 PYRROLIDINYL)ISOXAZOLE; METHACHOLINE; NICOTINE; NICOTINIC RECEPTOR; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BIOAVAILABILITY; COGNITIVE DEFECT; CONTROLLED STUDY; DOG; DRUG METABOLISM; DRUG SAFETY; GUINEA PIG; HEMODYNAMICS; HUMAN; HUMAN TISSUE; ILEUM; IN VITRO STUDY; INTRAVENOUS DRUG ADMINISTRATION; ISOTOPE LABELING; LIVER; MALE; MONKEY; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; SMOOTH MUSCLE CONTRACTION;

EID: 0030726757     PISSN: 02724391     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1098-2299(199705)41:1<31::AID-DDR4>3.0.CO;2-T     Document Type: Article

References (23)

1. Arneric SP, Maixner W, Long JP, Mott J, Barfknecht CF, Perez JA, Cannon JG (1982): Structure activity relationships of 2-amino-tetralin and 2-aminoindanes: Inhibitory neuro-effector mechanisms in isolated guinea pig ilea. Arch Int Pharmacodyn 258:84-99.
2. Arneric SP, Sullivan JP, Briggs CA, Donnelly-Roberts DL, Anderson DJ, Raszkiewicz JL, Hughes M, Cadman ED, Adams P, Garvey DS, Wasicak J, Williams M (1994): (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT-418): A novel cholinergic channel ligand with cognition enhancing and anxiolytic activity: In vitro activity. J Pharmacol Exp Ther 270:310-317.
3. Arneric SP, Anderson DA, Bannon AD, Brioni JD, Briggs CA, Buccafusco JJ, Decker MW, Donnelly-Roberts D, Gopalakrishnan M, Holladay MW, Sullivan JP (1995a): Preclinical pharmacology of ABT-418: A prototypical cholinergic channel activator for the treatment of Alzheimer's disease. CNS Drug Rev 1:1-26.
4. Arneric SP, Sullivan JP, Williams M (1995b): Neuronal nicotinic acetylcholine receptors: Novel targets for CNS therapeutics. In Bloom FE, Kupfer DJ (eds): Psychopharmacology: Fourth Generation of Progress. New York: Raven, pp 95-110.
5. Arneric, SP, Holladay MW, Sullivan JP (1996a): Cholinergic channel modulators as a novel therapeutic strategy for Alzheimer's disease. Exp Opin Invest Drugs 5:79-100.
6. Arneric SP, Bannon AW, Briggs CA, Brioni JD, Buccafusco JJ, Decker MW, Gopalakrishnan M, Holladay MW, Kyncl J, Lin NH, Marsh KC, Qiu YH, Radek R, Donnelly-Roberts DL, Sullivan JP, Williams M (1996b): ABT-089: an orally active cholinergin channel modulator (ChCM) with cognition enhancing and neuroprotective activity. In Becker R, Giacobini E, Robert P (eds): Alzheimer Disease: From Molecular Biology to Therapy. Birkhauser Boston, pp 287-292.
7. Benowitz NL (1996): Pharmacology of nicotine: Addiction and therapeutics. Ann Rev Pharmacol Toxicol 36:597-613.
8. Benowitz NL, Jacob P, Jones RT, Rosenberg J (1982): Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J Pharmacol Exp Ther 221:368-372.
9. Decker MW, Brioni JD, Sullivan JP, Buckley MJ, Radek RJ, Raszkiewicz JL, Kang C-H, Kim DJB, Giardina W, Wasicak J, Williams M, Arneric SP (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. J Pharmacol Exp Ther 270:317-324.
10. Decker MW, Bannon AW, Curzon P, Gunther K, Brioni JD, Holladay MW, Lin NH, Li Y, Daanen J, Buccafusco JJ, Prendergast MA, Jackson WA, Arneric SP (1997) Effects of ABT-089, a novel cholinergic channel modulator, on cognitive performance in rats and monkeys. J Pharmacol Exp Ther (in press).
11. Garvey DS, Wasicak JT Decker MW, Brioni JD, Buckley MJ, Sullivan JP, Carrera GM, Holladay MW, Arneric SP, Williams M (1994): Novel isoxazoles which interact with brain cholinergic channel receptors have intrinsic cognitive enhancing and anxiolytic activities. J Med Chem 37:1055-1059.
12. Hui Y-H, Carroll S, Marsh KC (1997): Development of a sensitive method for quantitation of ABT-089 in biological fluids following fluorescent labeling with NBD-F. J Chromatography (in press).
13. Jarvik ME (1991): Beneficial effects of nicotine. Br J Addict 86:571-575.
14. Lin NH, Gunn DE, Ryther KE, Garvey DS, Donnelly-Roberts DL, Decker MW, Brioni JD, Buckley MA, Rodrigues AD, Marsh KC, Anderson DJ, Buccafusco JJ, Prendergast MA, Sullivan JP, Williams M, Arneric SP, Holladay MW (1997): Structure-activity studies on ABT-089: An orally bioavailable 3-pyridyl ether cholinergic channel modulator with cognition enhancing properties. J Med Chem 40:385-390.
15. McGehee DS, Role LW (1995): Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Ann Rev Physiol 57:521-546.
16. McGehee DS, Heath MJS, Gelber S, Devay P, Role LW (1995): Nicotine enhancement of fast synaptic transmission in CNS by presynaptic receptors. Science 269:1692-1696.
17. Newhouse PA, Potter A, Corwin (1996): Acute administration of the cholinergic channel activator ABT-418 improves learning in Alzheimer's disease, Soc Res Nicotine Tobacco. Washington DC, March, A39.
18. Rodrigues AD, Ferrero JL, Amann MT, Rotert GA, Cepa SP, Surber BW, Machinist JM, Tich NR, Sullivan JP, Garvey DS, Fitzgerald M, Arneric SF (1994): The in vitro hepatic metabolism of ABT-418, a cholinergic channel activator, in rats, dogs, cynomolgus monkeys, and humans. Drug Metab Dispos 22:788-798.
19. Schievelbein H (1984): Nicotine, resorption and fate. In Balfour D. (ed): Nicotine and the Smoking Habit. Oxford: Pergamon Press, pp 1-15.
20. Sullivan JP, Anderson DJ, Briggs CA, Campbell JE, Donnelly-Roberts DL, Gopalakrishnan M, Gunn D, He Y, Holladay MW, McKenna D, Lin NH, Molinari E, Piattoni-Kaplan M, Xue I, Wonnacott S, Williams M, Arneric SP (1997): ABT-089: A potent and selective cholinergic channel modulator with neuroprotective properties. J Pharmacol Exp Ther (in press).
21. Taylor P (1990): Agents acting at the neuromuscular junction and autonomic ganglia. In Gilman AG, Rall TW, Nies AS, Taylor P (eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics. New York: Pergamon Press, pp. 166-186.
22. Williams M, Arneric SP (1996): Beyond the tobacco debate: dissecting out the therapeutic potential of nicotine. Expert Opinion in Investigational Drugs 5:1035-1045.
23. Williams M, Arneric SP (1997): Alzheimer's disease: Prospects for treatment in the next decade. In Brioni JD, Decker MW (eds): Pharmacological Treatment of Alzheimer's Disease. Molecular and Neurobiological Foundations. New York: Wiley-Liss, pp 525-542.