Pharmacokinetics and urinary excretion of DMXBA (GTS-21), a compound enhancing cognition

Biopharmaceutics and Drug Disposition

Volumn 19, Issue 3, 1998, Pages 147-151

  Mahnir, V ^a   Lin, B ^a   Prokai Tatrai, K ^a   Kem, W R ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

Alzheimer's disease; DMXBA; GTS 21; Nicotine; Nicotinic agonist; Pharmacokinetics

Indexed keywords

3 (2,4 DIMETHOXYBENZYLIDENE)ANABASEINE; NOOTROPIC AGENT;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ARTICLE; BLOOD BRAIN BARRIER; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG PROTEIN BINDING; INTRAVENOUS DRUG ADMINISTRATION; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; PARTITION COEFFICIENT; PHARMACOKINETICS; RAT; URINARY EXCRETION;

ANIMALS; BENZYLIDENE COMPOUNDS; BRAIN; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; COGNITION DISORDERS; MALE; NICOTINIC AGONISTS; PYRIDINES; RATS; RATS, SPRAGUE-DAWLEY;

EID: 0031923575     PISSN: 01422782     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1099-081X(199804)19:3<147::AID-BDD77>3.0.CO;2-9     Document Type: Article

References (19)

1. P.J. Whitehouse, A.M. Martino, P.C. Antuono, P.R. Lowenstein, J.T. Coylo, D.L. Price and K.J. Kellar, Nicotinic acetylcholine binding in Alzheimor's disease. Brain Res., 371, 146-151 (1986).
2. D.M. Araujo, P. A. Lapchak, Y. Robitaille, S. Gauthier and R. Quirion, Differential alternation of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer's disease. J. Neurochem., 50, 1914-1923 (1988).
3. K. Sugaya, E. Giacobini, and V.A. Chiappinelli, Nicotinic acetylcholine receptor subtypes in human frontal cortex: changes in Alzheimer's disease. J. Neurosci. Res., 27, 349-359 (1990).
4. P.A. Newhouse and A. Potter, The role of nicotinic systems in the cognitive disorder of Alzheimer's disease. In Alzhcimer Disease: Therapeutic Strategies, E. Giacobini and R. Becker, (Eds), Birkhauser, Boston, pp. 191-195 (1994).
5. W.R. Kem, V.M. Mahnir and B. Lin, Interaction of DMXBA (GTS-21), a cognition-enhancing compound, with cholinergic receptors. Soc. Neurosci. Abstr., 20, 1134 (1994).
6. W.R. Kem, B.C. Abbott and R.M. Coates, Isolation and structure of hoplonemertine toxin. Toxicon, 9, 15-22 (1971).
7. R.L. Papke, C.M. de Fiebre and W.R. Kem, The subunit specific effects of novel anabaseine-derived nicotinic agents. In Alzheimer disease: Therapeutic Strategies, E. Giacobini and R. Becker (Eds), Birkhauser, Boston, pp. 206-211 (1994).
8. 125I]x-bungarotoxin receptor subtypes. Mol. Pharmacol., 47, 164-171 (1995).
9. D.S. Woodruff-Pak, Y.-T. Li and W.R. Kem, A nicotinic agonist (GTS-21), eyeblink classical conditioning, and nicotinic receptor binding in rabbit brain. Brain Res., 645, 309-317 (1994).
10. G.W. Arendash, G.J. Sengstock, P.R. Sanberg and W.R. Kem. Improved learning and memory in aged rats with chronic administration of the nicotinic receptor agonist GTS-21. Brain Res., 674, 252-259.
11. E.M. Meyer, C.M. de Fiebre, B.E. Hunter, C.E. Simpkins, N. Frauworth and N.E.C. de Fiebre, Effects of anabaseine-related analogs on rat brain nicotinic receptor binding and on avoidance behaviors. Drug Dev. Res., 31, 127-134 (1994).
12. E.J. Martin, D.S. Panickar, M.A. King, M. Deyrup, B.E. Hunter, G. Wang and E.M. Meyer, Cytoprotective actions of 2,4-dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons. Drug Dev. Res., 31, 135-141 (1994).
13. J.A. Zoltewicz, K. Prokai-Tatrai, L.B. Bloom and W.R. Kem, Long range transmission of polar effects in cholinergic 3- arylidene anabascines. Conformations calculated by molecular modelling. Heterocyclics, 35, 171-179.
14. B.V.R. Sastry, M.B. Chance, G. Singh, J.L. Horn and V.E. Janson, Distribution and retention of nicotine and its metabolite, cotinine, in the rat as a function of time. Pharmacology, 50, 128-136 (1995).
15. G.A. McPherson, Analysis of radioligand binding experiments: a collection of computer programs for the IBM PC. J. Pharmacol. Methods, 14, 213-228 (1985).
16. W.R. Kem, V.M. Mahnir, B. Lin and K. Prokai-Tatrai, Two primary GTS-21 metabolites are potent partial agonists at alpha7 nicotinic receptors expressed in the Xenopus oocyte. Soc. Neurosci. Abstr., 22, 268 (1996).
17. N.L. Benowitz, H. Porchet and P. Jacob. Pharmacokinetics, metabolism, and pharmacodynamics of nicotine. In Nicotine Psychopharmacology: Molecular, Cellular, and Behavioral Aspects, S. Wonnacott, M.A.H. Russell and I.P. Stolerman (Eds), Oxford University Press, Oxford, UK, pp. 112-157 (1990).
18. A. Leo, C. Hansch and D. Elkins, Partition coefficients and their uses. Chem. Rev., 71, 525-616 (1971).
19. D.R. Plowchalk, M.E. Anderson and J.D. deBethizy, A physiologically based pharmacokinetic model for nicotine disposition in the Sprague-Dawley rat. Toxicol. Appl. Pharmacol., 116, 177-188 (1992).