Two new potent neurotransmitter release enhancers, 10, 10-bis(4- pyridinylmethyl)-9(10H)-anthracenone and 10,10-bis(2-fluoro-4- pyridinylmethyl)-9(10H)-anthracenone: Comparison to linopirdine

Journal of Pharmacology and Experimental Therapeutics

Volumn 285, Issue 2, 1998, Pages 724-730

  Zaczek, R ^a   Chorvat, R J ^a   Saye, J A ^a   Pierdomenico, M E ^a   Maciag, C M ^a   Logue, A R ^a   Fisher, B N ^a   Rominger, D H ^a   Earl, R A ^a  

^a DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

10,10 BIS(2 FLUORO 4 PYRIDINYLMETHYL) 9(10H) ANTHRACENONE; 10,10 BIS(4 PYRIDINYLMETHYL) 9(10H) ANTHRACENONE; ACETYLCHOLINE; LINOPIRDINE; NEUROTRANSMITTER; NEUROTROPIC AGENT; UNCLASSIFIED DRUG;

ACETYLCHOLINE RELEASE; ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG EFFECT; DRUG POTENCY; MALE; NEUROTRANSMITTER RELEASE; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RAT;

ACETYLCHOLINE; ALZHEIMER DISEASE; ANIMALS; ANTHRACENES; DOSE-RESPONSE RELATIONSHIP, DRUG; INDOLES; MALE; POTASSIUM CHANNEL BLOCKERS; PYRIDINES; RATS; RATS, SPRAGUE-DAWLEY; RATS, WISTAR;

EID: 0031809240     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (19)

1. Aiken SP, Lampe BJ, Murphy PA and Brown BS (1995) Reduction of spike frequency adaptation and blockade of M-current in rat CA1 pyramidal neurons by linopiridine (DuP 996), a neurotransmitter release enhancer. Br J Pharmacol 115:1163-1168.
2. Aiken SP, Zaczek R and Brown BS (1996) Pharmacology of the Neurotransmitter Release Enhancer Linopirdine (DuP 996), and Insights into Its Mechanism of Action, in Advances in Pharmacology, vol 35, pp 349-384 (August JT, Anders MW, Murad F and Coyle JT eds), Academic Press, San Diego, CA.
3. Bodick N and Offen W (1996) The M1-selective agonist xanomeline improves both the cognitive deficits and behavioral symptoms of patients with mild to moderate Alzheimer's. Fifth International Conference on Alzheimer's Disease and Related Disorders, Abstr. 557, 1996.
4. Brioni JD, Curzon P, Buckley MJ, Arneric SP and Decker MW (1993) Linopirdine (DuP996) facilitates the retention of avoidance training and improves performance of septal-lesioned rats in the water maze. Pharmacol Biochem Behav 44:37-43.
5. Chorvat RJ, Earl RA and Zaczek R (1995) Acetylcholine release enhancing agents: potential therapeutics for Alzheimer's disease. Drugs Future 20:1145-1162.
6. Cook LNV, Steinfels GF, Rohrbach KW and DeNoble VJ (1990) Cognition enhancement by the acetylcholine releaser DuP 996. Drug Dev Res 19:301-314.
7. Earl RA, Myers MJ, Johnson AL, Scribner RM, Wuonola MA, Boswell GA, Wilkerson WW, Nickolson VJ, Tam SW, Brittelli DR, Chorvat RJ, Zaczek R, Cook L, Wang C, Zhang X, Lan R, Mi B and Wenting H (1992) Acetylcholine-releasing agents as cognition enhancers. Structure-activity relationships of pyridinyl pendant groups on selected core structures. Bioorganic Med Chem Lett 2:851-854.
8. Farlow M, Gracon SI, Hershey LA, Lewis KW, Sadowsky CH, Dolan-Ureno J for the Tacrine Study Group (1992) A controlled trial of tacrine in Alzheimer's disease. JAMA 268:2523-2529.
9. + ion permeabilities in the acetylcholine release enhancing effects of linopirdine (DuP 996) in rat cerebral cortical slices. J Pharm Exp Ther 271:891-897.
10. Marynowaki M, Maciag C, Rominger CM, Rominger D, Tam SW and Znczek R (1993) Effects of linopirdine (DuP 996) on hippocampal extracellular levels of acetylcholine in freely moving animals. Soc Neurosci Abstr 23:423.8.
11. Nickolson VJ, Tam SW, Meyers MJ and Cook L (1990) DuP996 (3,3(4-pyrindylmethyl)1-phenylindolin-2-one) enhances the stimulus evoked release of acetylcholine from rat brain in vitro and in vivo. Drug Dev Res 19:285-300.
12. Pieniaszek HJ Jr, Fiske WD, Saxton TD, Kim YS, Garner DM, Xilinas M and Martz R (1995) Single dose pharmacokinetic, safety and tolerance of linopirdine (DuP 996) in healthy young adults and elderly volunteers. J Clin Pharm 35:22-30.
13. Rakeetraw DC (1990) The metabolism of DuP 996 in rats. Third North American ISSX Meeting Abstr. 43.
14. Ramsey BG and Walker FA (1974) A linear relationship between substituted pyridine lone pair ionization potentials and pKa. J Am Chem Soc 96:3314-3316.
15. Rogers S (1996) Clinical profile of donepezil (E2020). Fifth International Conference on Alzheimer's Disease and Related Disorders. Abstr. 181.
16. Smith TM, Ramirez AD, Heck SD, Jasys VJ, Volkmann RA, Forman JT and Liston DR (1993) In vivo microdialysis and pharmacokinetic studies with DuP996. Soc Neurosci Abstr 19:423.11.
17. Wilkerson WW, Kergaye AA and Tam SW (1993) 3-Substituted, 3-(4-pyridinylmethyl)-1,3-dihydro-1-phenyl-2H-indol-2-ones as acetylcholine release enhancers: Synthesis and SAR. J Med Chem 36:2899-2907.
18. Wilkerson WW, Earl RA, Calabrese JC, Drummond S, Teleha CA, Voss ME and Zaczek R (1996) Acetylcholine release enhancers related to linopirdine: A structure-activity relationship study. II. Eur J Med Chem 31:319-330.
19. Zaczek R and Saydoff JA (1993) Depolarization activated releasers of transmitters as therapeutics for dementia: preclinical characterization of linopirdine (DuP 996). Curr Opinion Invest Drugs 2:1097-1104.