Preclinical profiling and safety studies of ABT-769: A compound with potential for broad-spectrum antiepileptic activity

Epilepsia

Volumn 46, Issue 9, 2005, Pages 1349-1361

  Giardina, William J ^a   Dart, Michael J ^a   Harris, Richard R ^a   Bitner, Robert S ^a   Radek, Richard J ^a   Fox, Gerard B ^a   Chemburkar, Sanjay R ^a   Marsh, Kennan C ^a   Waring, Jeffrey F ^a   Hui, Julia Y ^a   Chen, Jinhua ^a   Curzon, Peter ^a   Grayson, George K ^a   Komater, Victoria A ^a   Ku, Yiyin ^a   Lockwood, Mark ^a   Miner, Holly M ^a   Nikkel, Arthur L ^a   Pan, Jia Bao ^a   Pu, Yu Ming ^a   Wang, Lei ^a   Bennani, Youssef ^a,c   Durmuller, Niklaus ^b   Jolly, Robert ^a,d   Roux, Sylvain ^b   Sullivan, James P ^a   Decker, Michael W ^a   more..

^a ABBOTT LABORATORIES   (United States)

^b Porsolt and Partners   (France)

^c VERTEX PHARMACEUTICALS   (United States)

^d ELI LILLY AND COMPANY   (United States)

Author keywords

Absence seizures; ABT 769; Animal seizure models; Anticonvulsant drugs; Kindled amygdala seizures; Maximal electroshock; Pentylenetetrazol; Valproic acid

Indexed keywords

A 425760; ABT 769; ANTICONVULSIVE AGENT; CARBAMAZEPINE; DIAZEPAM; LAMOTRIGINE; N (2 AMINO 2 OXOETHYL)SPIRO[2.5]OCTANE 1 CARBOXAMIDE; PENTETRAZOLE; PHENYTOIN; TIAGABINE; TOPIRAMATE; UNCLASSIFIED DRUG; VALPROIC ACID; VIGABATRIN; ABT-769; DRUG DERIVATIVE; SPIRO COMPOUND;

ABSENCE; AMYGDALOID NUCLEUS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICONVULSANT ACTIVITY; ARTICLE; AVOIDANCE BEHAVIOR; BRAIN CORTEX; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFICACY; DRUG SAFETY; ELECTRIC SHOCK; FATTY ACID OXIDATION; FEMALE; IN VITRO STUDY; KINDLING; LIVER TOXICITY; MALE; MITOCHONDRIAL RESPIRATION; MOTOR COORDINATION; MOUSE; NEURAL TUBE DEFECT; NONHUMAN; PRIORITY JOURNAL; REPRODUCTIVE TOXICITY; ROTAROD TEST; SEIZURE; SPIKE; TERATOGENICITY; TONIC CLONIC SEIZURE; ANIMAL; ANIMAL BEHAVIOR; CHEMICALLY INDUCED DISORDER; COMPARATIVE STUDY; CONGENITAL MALFORMATION; DISEASE MODEL; DRUG EFFECT; DRUG SCREENING; EPILEPSY; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; LIVER MITOCHONDRION; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; RAT; SPECIES DIFFERENCE; SUBCUTANEOUS DRUG ADMINISTRATION; WISTAR RAT;

ABNORMALITIES, DRUG-INDUCED; AMYGDALA; ANIMALS; ANTICONVULSANTS; BEHAVIOR, ANIMAL; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; ELECTROSHOCK; EPILEPSY; EPILEPSY, ABSENCE; HUMANS; INJECTIONS, INTRAVENOUS; INJECTIONS, SUBCUTANEOUS; KINDLING, NEUROLOGIC; MALE; MICE; MITOCHONDRIA, LIVER; PENTYLENETETRAZOLE; RATS; RATS, WISTAR; SPECIES SPECIFICITY; SPIRO COMPOUNDS; VALPROIC ACID;

EID: 26944494217     PISSN: 00139580     EISSN: 15281167     Source Type: Journal    
DOI: 10.1111/j.1528-1167.2005.02905.x     Document Type: Article

References (33)

1. Loscher W. New visions in the pharmacology of anticonvulsion. Eur J Pharmacol 1998 342 : 1 13.
2. Loscher W. Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action. Progr Neurobiol 1999 58 : 31 59.
3. Silberstein SD. Valproic acid: clinical efficacy and use in other neurological disorders. In : Levy RH Mattson RH Meldrum BS, et al. eds. Antiepileptic drugs, 5th ed. Philadelphia : Lippincott Williams & Wilkins, 2002 : 818.
4. Swann AC. Valproic acid: clinical efficacy and use in psychiatric disorders. In : Levy RH Mattson RH Meldrum BS, et al. eds. Antiepileptic drugs, 5th ed. Philadelphia : Lippincott Williams & Wilkins, 2002 : 829.
5. Davis LL Ryan W Adinoff B, et al. Comprehensive review of the psychiatric uses of valproate. J Clin Psychopharmacol 2000, 20 ( suppl 1 1S 17S.
6. Loscher W. Pharmacological effects and mechanism of action. In : Loscher W, ed. Valproate. Basal : Birkhauser Verlag, 1999 : 7.
7. Radatz M Nau H. Toxicity. In : Loscher W, ed. Valproate. Basal : Birkhauser Verlag, 1999 : 91.
8. Isoherranen N Yagen B Spiegelstein O, et al. Anticonvulsant activity, teratogenicity and pharmacokinetics of novel valproyltaurinamide derivatives in mice. Br J Pharmacol 2003 139 : 755 64.
9. Spiegelstein O Chatterjie N Alexander G, et al. Teratogenicity of valproate conjugates with anticonvulsant activity in mice. Epilepsy Res 2003 57 : 145 52.
10. Tang W Palaty J Abbott FS. Time course of α-fluorinated valproic acid in mouse brain and serum and its effect on synaptosomal γ-aminobutyric acid levels in comparison to valproic acid. J Pharmacol Exp Ther 1997 282 : 1163 72.
11. Baldwin GS Abbott FS Nau H. Binding of a valproate metabolite to the trifunctional protein of fatty acid oxidation. FEBS Lett 1996 384 : 58 60.
12. Hadad S Bialer M. Pharmacokinetic analysis and antiepileptic activity of two new isomers of N-valproyl glycinamide. Biopharm Drug Dispos 1997 18 : 557 66.
13. Isoherranen N White HS Finnell RH, et al. Anticonvulsant profile and teratogenicity of N-methyl-tetramethylcyclopropyl carboxamide: a new antiepileptic drug. Epilepsia 2002 43 : 115 26.
14. Bennani YL Bunnelle WH Chang S, et al. Preparation of spirocyclopropyl amides and acids as anticonvulsants. U.S. Pat. Appl. Publ. US 2004077616A1.
15. 50 values. J Pharmacol Toxicol Methods 1998 40 : 81 5.
16. Peeters BWMM Spooren WPJM van Luijtelaar ELJM, et al. The WAG/Rij rat model for absence epilepsy: anticonvulsant drug evaluation. Neurosci Res Commun 1988 2 : 93 7.
17. Meldrum BS Durmuller N. Non-MNDA receptor antagonists and the development of amygdala kindling. Epilepsy Res Suppl 1996 12 : 283 91.
18. Otto DA Chatzidakis C Kaziba E, et al. Reciprocal effects of 5-(tetradecyloxy)-2-furoic acid on fatty acid oxidation. Arch Biochem Biophys 1985 242 : 23 31.
19. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976 72 : 248 54.
20. Khera KS. Common fetal aberrations and their teratologic significance: a review. Fund Appl Toxicol 1981 1 : 13 8.
21. Khera KS. Maternal toxicity: a possible etiological factor in embryo-fetal deaths and fetal malformations of rodent-rabbit species. Teratology 1985 31 : 129 53.
22. Collins TFX Welsh JJ Black TN, et al. Potential reversibility of skeletal effects in rats exposed in utero to caffeine. Food Chem Toxicol 1987 25 : 647 62.
23. Van Luijtelaar ELJM Coenen AML. The WAG/Rij model for generalized absence seizures. In : Manelis J Bental E Loeber JN Dreifuss FE, eds., Advances in epileptology. Vol 17. New York : Raven Press, 1989 : 78.
24. Lochard JS Levy RH. Valproic acid: reversibly acting drug¿ Epilepsia 1976 17 : 477 9.
25. Loscher W Honack D. Comparison of anticonvulsant efficacy of valproate during prolonged treatment with one and three daily doses or continuous ("controlled release") administration in a model of generalized seizures in rats. Epilepsia 1995 36 : 929 37.
26. White HS Woodhead JM Wilcox KS, et al. General principles: discover and preclinical development of antiepileptic drugs. In : Levy RH Mattson RH Meldrum BS, et al. eds. Antiepileptic drugs, 5th ed. Philadelphia : Lippincott Williams & Wilkins, 2002 : 36.
27. Coenen ALM Blezer EHM van Luijtelaar ELJM. Effects of the GABA uptake inhibitor tiagabine on electroencephalogram: spike wave discharges and behavior of rats. Epilepsy Res 1995 21 : 89 94.
28. Van Luijtelaar ELJM Drinkenburg WHIM van Rijn CM, et al. Rat models of genetic absence epilepsy: what do EEG spike-wave discharges tell us about drug effects¿ Methods Find Exp Clin Pharmacol 2002 24 ( suppl D 65 70.
29. Van Rijn CM Weyn Banningh EW Coenen AM. Effects of lamotrigine on absence seizures in rats. Pol J Pharmacol 1994 46 : 467 70.
30. Constanti RE Ferreri G Citraro R, et al. Nifedipine affects the anticonvulsant activity of topiramate in various animal models of epilepsy. Neuropharmacology 2004 46 : 865 78.
31. Ehlers K Sturje H Meeker HJ, et al. Valproic acid-induced spina bifida: a mouse model. Teratology 1992 45 : 145 54.
32. Beghi E. The use of anticonvulsants in neurological conditions other than epilepsy: a review of the evidence from randomized controlled trials. CNS Drugs 1999 11 : 61 82.
33. Lopes da Silva F Post RM. Evaluation and prediction of effects of antiepileptic drugs in a variety of other CNS disorders. Epilepsy Res 2002 50 : 191 3.