ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys
Abstract
ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride], a novel ligand at neuronal nicotinic acetylcholine receptors with reduced adverse effects and improved oral bioavailability relative to (-)-nicotine, was tested in a variety of cognitive tests in rats and monkeys. Administered acutely, ABT-089 only marginally improved the spatial discrimination water maze performance of septal-lesioned rats. However, more robust improvement (45% error reduction on the last training day) was observed when ABT-089 was administered continuously via subcutaneous osmotic pumps (minimum effective dose: 1.3 micromol/kg/day). Continuous infusion of (-)-nicotine produced comparable improvement in the spatial discrimination water maze performance of septal-lesioned rats, but a 40-fold higher dose of (-)-nicotine was required (62 micromol/kg/day). Continuous infusion of ABT-089 to aged rats enhanced spatial learning in a standard Morris water maze, as indexed by spatial bias exhibited during a probe trial conducted after 4 days of training, but not when they were subsequently trained in a two-platform spatial discrimination water maze. The compound induced a small impairment in young rats on the standard water maze, but not on the two-platform task. A probe trial conducted after additional training in the standard water maze revealed no age or drug effects. ABT-089 did not affect performance of either the aged or young rats during inhibitory (passive) avoidance training. Also, continuous infusion of ABT-089 did not affect responses to acoustic startle or prepulse inhibition of acoustic startle in young, aged or septal-lesioned rats and did not affect locomotor activity in either sham-lesioned or septal-lesioned rats. In monkeys, acute administration of ABT-089 modestly improved the delayed matching-to-sample performance of mature, adult monkeys and more robustly improved performance in aged monkeys. Improved performance in the aged monkeys was restricted to the longest delay intervals and was not accompanied by changes in response latencies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both ABT-089 and ABT-107 enhance learning in naive animals.
“Both ABT-089 and ABT-107 enhance learning in naive animals (Decker et al., 1997;Bitner et al., 2010).”
From Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors (2014) · cites this paper as Decker et al., 1997
Cites
Alzheimer's Disease: A Disorder of Cortical Cholinergic Innervation
Coyle, J. T., Price, D. L., & DeLong, M. R. (1983) · Science · doi:10.1126/science.6338589 · Cited by 3,050 · see citing works
A rapid radiochemical method for the determination of choline acetyltransferase
Fonnum, F. (1975) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1975.tb11895.x · Cited by 2,358 · see citing works
Gallagher, M., Burwell, R. D., & Burchinal, M. A. (2015) · Behavioral Neuroscience · doi:10.1037/bne0000080 · Cited by 861 · see citing works
Gallagher, M., Burwell, R. D., & Burchinal, M. (1993) · Behavioral Neuroscience · doi:10.1037/0735-7044.107.4.618 · Cited by 675 · see citing works
Memory and cognitive function in man
Drachman, D. A. (1977) · Neurology · doi:10.1212/wnl.27.8.783 · Cited by 619 · see citing works
Packard, M. G., & McGaugh, J. L. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.3.439 · Cited by 555 · see citing works
Packard, M. G., & McGaugh, J. L. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.3.439 · Cited by 528 · see citing works
Nicotinic systems and cognitive function
Levin, E. D. (1992) · Psychopharmacology · doi:10.1007/bf02247415 · Cited by 511 · see citing works
Jones, G., Sahakian, B. J., Levy, R., Warburton, D. M., & Gray, J. A. (1992) · Psychopharmacology · doi:10.1007/bf02247426 · Cited by 476 · see citing works
Short-term memory in the rhesus monkey: Disruption from the anti-cholinergic scopolamine
Bartus, R. T., & Johnson, H. R. (1976) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(76)90286-0 · Cited by 334 · see citing works
Kesner, R., Bolland, B. L., & Dakis, M. (1993) · Experimental Brain Research · doi:10.1007/bf00229361 · Cited by 325 · see citing works
Intravenous nicotine in Alzheimer's disease: a pilot study
NEWHOUSE, P. A., Sunderland, T., Tariot, P. N., Blumhardt, C. L., Weingartner, H., Mellow, A. M., & Murphy, D. L. (1988) · Psychopharmacology · doi:10.1007/bf00174504 · Cited by 308 · see citing works
Decker, M. W., Brioni, J. D., Bannon, A. W., & Arnerić, S. P. (1995) · Life Sciences · doi:10.1016/0024-3205(94)00488-e · Cited by 256 · see citing works
Self-citationBeatty, W. W., Butters, N., & Janowsky, D. S. (1986) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(86)90772-7 · Cited by 249 · see citing works
Sahakian, B. J., Owen, A. M., Morant, N. J., Eagger, S. A., Boddington, S., Crayton, L., Crockford, H. A., Crooks, M., Hill, K., & Levy, R. (1993) · Psychopharmacology · doi:10.1007/bf02244644 · Cited by 226 · see citing works
Swerdlow, N. R., & Geyer, M. A. (1993) · Behavioral Neuroscience · doi:10.1037//0735-7044.107.1.104 · Cited by 217 · see citing works
Scopolamine effects on memory retention in mice: A model of dementia?
Flood, J. F., & Cherkin, A. (1986) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(86)90750-8 · Cited by 213 · see citing works
Arendash, G. W., Sengstock, G. J., Sanberg, P. R., & Kem, W. R. (1995) · Brain Research · doi:10.1016/0006-8993(94)01449-r · Cited by 198 · see citing works
Nicotine patches in Alzheimer's disease: Pilot study on learning, memory, and safety
Wilson, A. L., Langley, L. K., Monley, J., Bauer, T., Rottunda, S. J., McFalls, E. O., Kovera, C. A., & McCarten, J. R. (1995) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)00043-v · Cited by 196 · see citing works
Swerdlow, N. R., & Geyer, M. A. (1993) · Behavioral Neuroscience · doi:10.1037/0735-7044.107.1.104 · Cited by 192 · see citing works
Decker, M. W., Brioni, J. D., Sullivan, J. P., Buckley, M. J., Radek, R. J., Raszkiewicz, J. L., Kang, C. H., Kim, D. J., Giardina, W. J., & Wasicak, J. T. (1994) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22339-4 · Cited by 180 · see citing works
Self-citationBammer, G. (1982) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(82)90041-0 · Cited by 172 · see citing works
Tacrine: A pharmacological review
Freeman, S. E., & Dawson, R. M. (1991) · Progress in Neurobiology · doi:10.1016/0301-0082(91)90002-i · Cited by 168 · see citing works
Buccafusco, J. J., & Jackson, W. J. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90102-p · Cited by 164 · see citing works
Self-citationAraujo, D., Lapchak, P. A., Meaney, M., Collier, B., & Quirion, R. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-09-03069.1990 · Cited by 155 · see citing works
Acute nicotinic blockade produces cognitive impairment in normal humans
NEWHOUSE, P. A., Potter, A., Corwin, J., & Lenox, R. H. (1992) · Psychopharmacology · doi:10.1007/bf02247425 · Cited by 149 · see citing works
Nicotine enhances delayed matching-to-sample performance by primates
Elrod, K., Buccafusco, J. J., & Jackson, W. J. (1988) · Life Sciences · doi:10.1016/0024-3205(88)90318-9 · Cited by 142 · see citing works
Self-citationEffects of nicotine on spatial memory deficits in rats with septal lesions
Decker, M. W., Majchrzak, M. J., & Anderson, D. J. (1992) · Brain Research · doi:10.1016/0006-8993(92)90485-r · Cited by 140 · see citing works
Self-citationHodges, H., Allen, Y. S., Sinden, J. D., et al. (1991) · Behavioural Brain Research · doi:10.1016/s0166-4328(05)80048-8 · Cited by 138 · see citing works
Scopolamine amnesia of passive avoidance: A deficit of information acquisition
Rush, D. K. (1988) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(88)90938-7 · Cited by 131 · see citing works
Decker, M. W., Curzon, P., & Brioni, J. D. (1995) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1995.1055 · Cited by 126 · see citing works
Self-citationWoodruff‐Pak, D. S., Li, Y.-T., & Kem, W. R. (1994) · Brain Research · doi:10.1016/0006-8993(94)91665-9 · Cited by 119 · see citing works
Self-citationAlzheimer Disease: from Molecular Biology to Therapy
Giacobini, E. (1997) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(97)85593-x · Cited by 115 · see citing works
Nicotine enhances morris water maze performance of young and aged rats
Socci, D. J., Sanberg, P. R., & Arendash, G. W. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00091-r · Cited by 115 · see citing works
Effects of lobeline, a nicotinic receptor agonist, on learning and memory
Decker, M. W., Majchrzak, M. J., & Arnerić, S. P. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90508-q · Cited by 107 · see citing works
Self-citationMeyer, E. M., de Fiebre, C. M., Hunter, B. E., Simpkins, C. E., Frauworth, N., & de Fiebre, N. E. C. (1994) · Drug Development Research · doi:10.1002/ddr.430310207 · Cited by 103 · see citing works
Buccafusco, J. J., Jackson, W. J., Terry, A. V., Marsh, K. C., Decker, M. W., & Arnerić, S. P. (1995) · Psychopharmacology · doi:10.1007/bf02311172 · Cited by 100 · see citing works
Self-citationBerry CA: Effect of cholinergic drugs on passive avoidance in the mouse.
Sl, D. (1967) · PubMed · Cited by 91 · see citing works
Effects of nicotinic acetylcholine receptor ligands on behavioral vigilance in rats
Turchi, J. N., Holley, L. A., & Sarter, M. F. (1995) · Psychopharmacology · doi:10.1007/bf02245840 · Cited by 83 · see citing works
Tilson, H. A., McLamb, R. L., Shaw, S., Rogers, B. C., Pediaditakis, P., & Cook, L. L. (1988) · Brain Research · doi:10.1016/0006-8993(88)91326-1 · Cited by 80 · see citing works
Sullivan, J. P., Donnelly‐Roberts, D. L., Briggs, C. A., Anderson, D. J., Gopalakrishnan, M., Xue, I. C., Piattoni-Kaplan, M., Molinari, E. J., Campbell, J. E., McKenna, D. G., et al. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37014-4 · Cited by 79 · see citing works
Self-citationCHOLINERGIC ‘BLOCKADE’ AS A MODEL OF THE COGNITIVE DEFICITS IN ALZHEIMER'S DISEASE
CHRISTENSEN, H., MALTBY, N., JORM, A. F., CREASEY, H., & BROE, G. A. (1992) · Brain · doi:10.1093/brain/115.6.1681 · Cited by 74 · see citing works
Effects of ABT-418, a novel cholinergic channel ligand, on place learning in septal-lesioned rats
Decker, M. W., Curzon, P., Brioni, J. D., et al. (1994) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)90323-9 · Cited by 72 · see citing works
Self-citationDecker, M. W., & Majchrzak, M. J. (1992) · Psychopharmacology · doi:10.1007/bf02245267 · Cited by 69 · see citing works
Self-citationLin, N.-H., Gunn, D. E., Ryther, K. B., Garvey, D. S., Donnelly-Roberts, D. L., Decker, M. W., Brioni, J. D., Buckley, M. J., Rodrigues, A. D., Marsh, K. G., et al. (1997) · Journal of Medicinal Chemistry · doi:10.1021/jm960233u · Cited by 67 · see citing works
Self-citationBrioni, J. D., & Arnerić, S. P. (1993) · Behavioral and Neural Biology · doi:10.1016/0163-1047(93)91159-k · Cited by 63 · see citing works
Self-citationNovel Approaches to the Treatment of Alzheimer’s Disease
Meyer, E. M., Simpkins, J. W., & Yamamoto, J. (1989) · Advances in behavioral biology · doi:10.1007/978-1-4684-5727-8 · Cited by 61 · see citing works
Cholinergic drugs regulate passive avoidance performance via the amygdala.
Riekkinen, P. J., Riekkinen, M., & Sirviö, J. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39599-6 · Cited by 60 · see citing works
Scopolamine reversal of nicotine enhanced delayed matching-to-sample performance in monkeys
Terry, A. V., Buccafusco, J. J., & Jackson, W. J. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90141-f · Cited by 60 · see citing works
Self-citationPrendergast, M., Terry, A. V., Jackson, W. J., Marsh, K. C., Decker, M. W., Arnerić, S. P., Buccafusco, J. J., & Terry, A. V. (1997) · Psychopharmacology · doi:10.1007/s002130050240 · Cited by 43 · see citing works
Self-citationEffects of intraseptal injection of 192-IgG-saporin in mature and aged Long-Evans rats
Bannon, A. W., Curzon, P., Gunther, K. L., et al. (1996) · Brain Research · doi:10.1016/0006-8993(95)01568-x · Cited by 41 · see citing works
Self-citationRiekkinen, P. J., Riekkinen, M., Sirviö, J., & Riekkinen, P. J. (1992) · Brain Research · doi:10.1016/0006-8993(92)90086-o · Cited by 36 · see citing works
Widzowski, D., CREGAN, E. F., & Bialobok, P. (1994) · Drug Development Research · doi:10.1002/ddr.430310105 · Cited by 33 · see citing works
Jackson, W. J., Elrod, K., & Buccafusco, J. J. (1989) · Advances in behavioral biology · doi:10.1007/978-1-4684-5727-8_5 · Cited by 32 · see citing works
Self-citationEFFECT OF CHOLINERGIC DRUGS ON PASSIVE AVOIDANCE IN THE MOUSE
Sl, D., & Berry, C. A. (1967) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)27793-x · Cited by 25 · see citing works
Arnerić, S. P., Holladay, M. W., & Sullivan, J. P. (1996) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.5.1.79 · Cited by 24 · see citing works
Self-citationSpecific disruption of spatial behaviour in rats by central muscarinic receptor blockade
Willner, P., Wise, D., & Ellis, T. (1986) · Psychopharmacology · doi:10.1007/bf00181247 · Cited by 17 · see citing works
NEWHOUSE, P. A., Potter, A. S., Corwin, J., et al. (1994) · Drug Development Research · doi:10.1002/ddr.430310111 · Cited by 17 · see citing works
Brioni, J. D., Kim, D. J. B., O'Neill, A. B., Brodie, M. S., Decker, M. W., & Arnerić, S. P. (1997) · Drug Development Research · doi:10.1002/(sici)1098-2299(199703)40:3 · Cited by 3 · see citing works
Self-citationLin, N., Gunn, D., Ryther, K. B., et al. (1997) · ChemInform · doi:10.1002/chin.199719153 · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Guidelines on nicotine dose selection for in vivo research
Matta, S. G., Balfour, D. J., Benowitz, N. L., Boyd, R. T., Buccafusco, J. J., Caggiula, A. R., Craig, C. R., Collins, A. C., Damaj, M. I., Donny, E. C., et al. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0441-0 · Cited by 824 · see citing works
Self-citationWilens, T. E., & Decker, M. W. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.002 · Cited by 164 · see citing works
Self-citationParikh, V., Ji, J., Decker, M. W., & Sarter, M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5712-09.2010 · Cited by 133 · see citing works
Self-citationAnimal models of Alzheimer disease: historical pitfalls and a path forward
Cavanaugh, S. E. (2014) · ALTEX · doi:10.14573/altex.1310071 · Cited by 132 · see citing works
Parikh, V., Man, K., Decker, M. W., & Sarter, M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5251-07.2008 · Cited by 127 · see citing works
Self-citationWilens, T. E., Verlinden, M. H., Adler, L. A., Wozniak, P. J., & West, S. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.029 · Cited by 123 · see citing works
Rueter, L. E., Anderson, D. J., Briggs, C. A., Donnelly‐Roberts, D. L., Gintant, G. A., Gopalakrishnan, M., Lin, N., Osinski, M. A., Reinhart, G. A., Buckley, M. J., et al. (2004) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2004.tb00011.x · Cited by 70 · see citing works
Self-citationSelectivity of ABT-089 for α4β2* and α6β2* nicotinic acetylcholine receptors in brain
Marks, M. J., Wageman, C. R., Grady, S. R., Gopalakrishnan, M., & Briggs, C. A. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.05.022 · Cited by 30 · see citing works
Yohn, N. L., Turner, J. R., & Blendy, J. A. (2014) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.211706 · Cited by 28 · see citing works
- Authors
- Decker, M. W., Bannon, A. W., Curzon, P., Gunther, K. L., Brioni, J. D., Holladay, M. W., Lin, N.-H., Li, Y., Daanen, J. F., Buccafusco, J. J., Prendergast, M. A., Jackson, W. J., & Arneric, S. P.
- Affiliations
- Abbott (United States) (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 283
- Issue
- 1
- Pages
- 247-258
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2188389009
- Cited by
- 88
- References
- 60
- Citations by year
- 2026: 1 · 2024: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 1 · 2015: 3 · 2014: 9 · 2013: 2 · 2012: 2
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- nicotinic agonists, cognitive enhancement, spatial learning, aging, septal lesions, water maze, passive avoidance, prepulse inhibition, acoustic startle response, aged monkeys, aged rats
- MeSH terms
- Animals, Avoidance Learning, Cognition, Discrimination Learning, Female, Ion Channels, Macaca nemestrina, Male, Nicotine, Pyridines, Pyrrolidines, Receptors, Nicotinic, Cholinergic Agents, Maze Learning, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
