Stereoselective pharmacodynamic and pharmacokinetic analysis of sec -butylpropylacetamide (SPD), a new CNS-Active derivative of valproic acid with unique activity against status epilepticus

Journal of Medicinal Chemistry

Volumn 56, Issue 16, 2013, Pages 6467-6477

  Hen, Naama ^a   Shekh Ahmad, Tawfeeq ^a   Yagen, Boris ^a,b   McDonough, John H ^c   Finnell, Richard H ^d   Wlodarczyk, Bogdan ^d   Bialer, Meir ^a,b  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^c US ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE   (United States)

^d UNIVERSITY OF TEXAS AT AUSTIN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICONVULSIVE AGENT; BUTYLPROPYLACETAMIDE; PILOCARPINE; UNCLASSIFIED DRUG; VALPROIC ACID DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFICACY; DRUG HALF LIFE; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; EPILEPTIC STATE; MAXIMUM PLASMA CONCENTRATION; MOUSE; MOUSE STRAIN; NEURAL TUBE DEFECT; NEUROTOXICITY; NONHUMAN; PHARMACODYNAMICS; RACEMIC MIXTURE; RAT; STEREOCHEMISTRY; STEREOISOMERISM; TERATOGENICITY; TIME TO MAXIMUM PLASMA CONCENTRATION;

ACETAMIDES; ANIMALS; ANTICONVULSANTS; DISEASE MODELS, ANIMAL; RATS; SOMAN; STATUS EPILEPTICUS; STEREOISOMERISM; TERATOGENS; VALPROIC ACID;

EID: 84883200078     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4007565     Document Type: Article

References (42)

1. 50 values of antiepileptic drugs in mice and rats and their therapeutic doses and plasma levels Epilepsy Behav. 2004, 5, 866-872
2. Rogawski, M. A. Molecular targets versus models for new antiepileptic drug discovery Epilepsy Res. 2006, 68, 22-28
3. Bialer, M.; White, H. S. Key factors in the discovery and development of new antiepileptic drugs Nat. Rev. Drug Discovery 2010, 9, 68-82
4. Bersudsky, Y.; Applebaum, J.; Gaiduk, Y.; Sharony, L.; Mishory, A.; Podberezsky, A.; Agam, G.; Belmaker, R. H. Valnoctamide as a valproate substitute with low teratogenic potential in mania: a double-blind, controlled, add-on clinical trial Bipolar Disord. 2010, 12, 376-382
5. Bialer, M.; Yagen, B. Valproic acid-second generation Neurotherapeutics. 2007, 4, 130-137
6. Bialer, M.; Johannessen, S. I.; Levy, R. H.; Perucca, E.; Tomson, T.; White, H. S. Progress report on new antiepileptic drugs: a summary of the Eleventh EILAT Conference (EILAT XI) Epilepsy Res. 2013, 103, 2-13
7. Barel, S.; Yagen, B.; Schurig, V.; Soback, S.; Pisani, F.; Perucca, E.; Bialer, M. Stereoselective pharmacokinetic analysis of valnoctamide in healthy subjects and in patients with epilepsy Clin. Pharmacol. Ther. 1997, 61, 442-449
8. White, H. S.; Alex, A. B.; Pollock, A.; Hen, N.; Shekh-Ahmad, T.; Wilcox, K. S.; McDonough, J. H.; Stables, J. P.; Kaufmann, D.; Yagen, B.; Bialer, M. A new derivative of valproic acid amide possesses a broad-spectrum antiseizure profile and unique activity against status epilepticus and organophosphate neuronal damage Epilepsia 2012, 53, 134-146
9. Pouliot, W.; Bialer, M.; Hen, N.; Shekh-Ahmad, T.; Kaufmann, D.; Yagen, B.; Ricks, K.; Roach, B.; Nelson, C.; Dudek, F. E. Electrographic analysis of the effect of sec -butyl-propylacetamide on pharmacoresistant status epilepticus Neuroscience 2013, 231, 145-156
10. Finney, D. J. Statistical logic in the monitoring of reactions to therapeutic drugs Methods Inf. Med. 1971, 10, 237-245
11. Jones, R. S.; Heinemann, U. Synaptic and intrinsic response of medical entorhinal cortical cells in normal and magnesium-free medium in vitro J. Neurophysiol. 1988, 59, 1476-1496
12. Smith-Yockman, M. D.; White, H. S.; Wlicox, K. Characterization of "phenytoin-resistant" spontaneous bursting in the medial enorhinal cortex (mEC) in brain slices obtained from kianaic acid (KA)-treated rats Epilepsia 2003, 44 (Suppl. 9) 202; Abstract 2078
13. Dreier, J. P.; Henemann, U. Late low magnesium-induced epileptiform activity in rat entorinal cortex sliced becomes insensitive to anticonvulsant valproic acid Neurosci. Lett. 1990, 119, 68-70
14. Altman, P. L.; Dittmer, D. S. Biology Data Book, 2 nd ed.; Federation of American Societies for Experimental Biology: Bethesda, MD, 1974; Vol. 3, pp 1702-1710.
15. Nalivaeva, N. N.; Belyaev, N. C. D.; Turner, A. J. Sodium valproate: an old drugs with new roles Trends Pharmacol. Sci. 2009, 30, 509-514
16. Bialer, M. Why are antiepileptic drugs used for nonepileptic conditions? Epilepsia 2012, 50 (Suppl. 7) 26-33
17. Meador, K. J. Effect of in-utero antiepileptic drug exposure Epilepsy Curr. 2008, 8, 144-147
18. Kaufmann, D.; Yagen, B.; Minert, A.; Wlodarczk, B.; Finnell, R. H.; Schurig, V.; Devor, M.; Bialer, M. Evaluation of antiallodynic, teratogenic and pharmacokinetic profile of stereoisomers of valnoctamide, an amide derivative of a chiral isomer of valproic acid Neuropharmacology 2010, 52, 1228-1236
19. Spiegelman, O.; Yagen, B.; Levy, R. H.; Finnell, R. H.; Bennet, G. D.; Roeder, M.; Schurig, V.; Bialer, M. Strereoselective pharmacokinetics and pharmacodynamics of propylisopropyl acetamide-a CNS-active chiral amide derivative of valproic acid Pharm. Res. 1999, 16, 1582-1588
20. Jones, D. M.; Esmaeil, N.; Maren, S.; Macdonald, R. L. Characterization of pharmacoresistance to benzodiazepines in the rat Li-pilocarpine model of status epilepticus Epilepsy Res. 2002, 50, 301-312
21. Agranat, I.; Caner, H.; Caldwell, J. Putting chirality to work: the strategy of chiral switches Nat. Rev. Drug Discovery 2002, 1, 753-768
22. Kupfer, A.; Robaers, R. K.; Sclenker, S.; Branch, A. Stereoselective metabolism of mephenytoin in man J. Pharmacol. Exp. Ther. 1981, 218, 193-199
23. Levy, R. H.; Boddy, A. V. Stereoselectivity in pharmacokinetics: a general theory Pharm. Res. 1991, 8, 551-555
24. Karim, A.; Piergies, A. Verapamil stereoisomers: enantiomer ratio in plasma dependent on peak concentrations, oral input rate, or both Clin. Pharmacol. Ther. 1995, 58, 174-184
25. Hubbard, W. K. FDA policy on period of marketing exclusivity for newly approved drug products with enantiomer active ingredients; request for comments Fed. Regist. 1997, 62, 2167-2169
26. Tucker, G. T. Chiral switches Lancet 2003, 55, 1085-1087
27. Kaufmann, D.; Bialer, M.; Shimshoni, J. A.; Devor, M.; Yagen, B. Synthesis and evaluation of antiallodynic and anticonvulsant activity of novel amide and urea derivatives of valproic acid analogues J. Med. Chem. 2009, 52, 7236-7248
28. Pessah, N.; Bialer, M.; Wlodarczyk, B.; Finnell, R. H.; Yagen, B. Alpha-fluoro-2,2,3,3-tetramethylcyclopropanecarboxamide, a novel potent anticonvulsant derivative of a cyclic analogue of valproic acid J. Med. Chem. 2009, 52, 2233-2242
29. Rowland, M.; Tozer, T. N. Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications; Lippincott William & Wilkins: Philadelphia, PA, 2011; pp 49-71.
30. Lothman, E. W. Seizure circuits in the hippocampus and associated structures Hippocampus 1994, 4, 286-290
31. White, H. S.; Johnson, M.; Wolf, H. H.; Kupferberg, H. J. The early identification of anticonvulsant activity: role of the maximal electroshock and subcutaneous pentylenetetrazol seizure models Ital. J. Neurol. Sci. 1995, 16, 73-77
32. Smith, M.; Wilcox, K. S.; White, H. S. Discovery of antiepileptic drugs Neurotherapeutics 2007, 4, 12-17
33. Woodbury, L. A.; Davenport, V. D. Design and use of a new electroshock seizure apparatus, and analysis of factors altering seizure threshold and pattern Arch. Int. Pharmacodyn. Ther. 1952, 92, 97-107
34. Toman, J. E.; Everett, G. M.; Richards, R. K. The search for new drugs against epilepsy Tex. Rep. Biol. Med. 1952, 10, 96-104
35. Barton, M. E.; Klein, B. D.; Wolf, H. H.; White, H. S. Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy Epilepsy Res. 2001, 47, 217-227
36. Bliss, C. The Statistics of Bioassay with Special Reference to the Vitamins. In Vitamin Methods; Academic Press: New York, 1952; pp 445-628.
37. Shih, T. M.; Koviak, T. A.; Capacio, B. R. Anticonvulsants for poisoning by the organophosphorus compound soman: pharmacological mechanisms Neurosci. Biobehav. Rev. 1991, 15, 349-362
38. McDonough, J. H.; Shih, T. M. Pharmacological modulation of soman-induced seizures Neurosci. Biobehav. Rev. 1991, 17, 203-215
39. Shih, T. M.; McDonough, J. H. Neurochemical mechanisms in soman-induced seizures J. Appl. Toxicol. 1991, 17, 255-264
40. Finnell, R. H.; Bennett, G. D.; Karras, S. B.; Mohl, V. K. Common hierarchies of susceptibility to the induction of neural tube defects in mouse embryos by valproic acid and its 4-propyl-4-pentenoic acid metabolite Teratology 1988, 38, 313-320
41. Finnell, R. H.; Bielec, B.; Nau, H. Anticonvulsant Drugs: Mechanisms and Pathogenesis of Teratogenicity. In Drug Toxicity in Embryonic Development: Advances in Understanding Mechanisms of Birth Defects; Kavlock, R. J.; Daston, G. P., Eds.; Handbook of Experimental Pharmacology, Vol. 124; Springer-Verlag: Berlin, 1997; Vol. II, pp 121-159.
42. Sobol, E.; Yagen, B.; White, S. H.; Wilcox, K. S.; Lamb, J. G.; Pappo, O.; Wlodarczyk, B. J.; Finnell, R. H.; Bialer, M. Preclinical evaluation of 2,2,3,3-tetramethylcyclopropanecarbonyl-urea, a novel, second generation to valproic acid, antiepileptic drug Neuropharmacology 2006, 51, 933-946