Synthesis and anticonvulsant evaluation of dimethylethanolamine analogues of valproic acid and its tetramethylcyclopropyl analogue

Epilepsy Research

Volumn 98, Issue 2-3, 2012, Pages 238-246

  Shekh Ahmad, Tawfeeq ^a   Bialer, Meir ^a   Yavin, Eylon ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Anticonvulsant activity; Maximal electroshock seizure test; Pharmacokinetic pharmacodynamic correlation; Subcutaneous metrazol seizure test; Valproic acid esteric and amide deraivatives

Indexed keywords

2,2,3,3 TETRAMETHYLCYCLOPROPANECARBOXYLIC ACID DERIVATIVE; DEVAMIDE; N,N DIMETHYLETHANOLAMINE 2,2,3,3 TETRAMETHYLCYCLOPROPIONATE; N,N DIMETHYLETHANOLAMINE VALPROATE; UNCLASSIFIED DRUG; VALPROIC ACID; VALPROIC ACID DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICONVULSANT ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE; DRUG EFFICACY; DRUG HALF LIFE; DRUG HYDROLYSIS; DRUG MONITORING; DRUG POTENCY; DRUG SCREENING; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ELECTRIC SHOCK; HIPPOCAMPUS; KINDLING; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; ANTICONVULSANTS; BRAIN WAVES; CONVULSANTS; CYCLOPROPANES; DEANOL; DISEASE MODELS, ANIMAL; ELECTROENCEPHALOGRAPHY; ELECTROSHOCK; EPILEPSY; HIPPOCAMPUS; KINDLING, NEUROLOGIC; MALE; MICE; PENTYLENETETRAZOLE; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; VALPROIC ACID;

EID: 84856504238     PISSN: 09201211     EISSN: 18726844     Source Type: Journal    
DOI: 10.1016/j.eplepsyres.2011.10.005     Document Type: Article

References (30)

1. Adkison K.D.K., Arturu A.A., Powers K.M., Shen D.D. Distribution of probenecid-sensitive anion transport processes at the brain capillary endotheium and choroid plexus to the efficient efflux of valproic acid from the central nervous system. J. Pharmacol. Exp. Ther. 1994, 268:797-805.
2. Bialer M., Johannessen S.I., Kupferberg H.J., Levy R.H., Loiseau P., Perucca E. Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI). Epilepsy Res. 2002, 51:31-71.
3. 50 values of antiepileptic drugs in mice and rats and their therapeutic doses and plasma levels. Epilepsy Behav. 2004, 5:866-872.
4. Bialer M., Yagen B. Valproic acid: second generation. Neurotherapeutics 2007, 4:130-137.
5. Bialer M., White H.S. Key factors in the discovery and development of new antiepileptic drugs (AEDs). Nat. Rev. Drug Discov. 2010, 9:68-83.
6. Blotnik S., Bergman F., Bialer M. Disposition of valpromide, valproic acid, and valnoctamide in the brain, liver, plasma, and urine of rats. Drug Metab. Dispos. 1996, 24:560-564.
7. Blotnik S., Bergman F., Bialer M. Disposition of tetramethylcyclopropane analogues of valpromide in the brain, liver, plasma and urine of rats. Eur. J. Pharm. Sci. 1998, 6:93-98.
8. Bresudsky Y., Applebaum J., Gaiduk I., Sharony Y., Mishory A., Poberezsky 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.
9. Cornford E.M., Braun L.D., Oldendorf W.H. Carrier mediated blood-brain-barrier transport of choline and certain choline analogs. J. Neurochem. 1978, 30:299-308.
10. Haberer L.J., Pollack G.M. Disposition and protein binding of valproic acid in the developing rat. Drug Metab. Dispos. 1994, 22:113-119.
11. Ichimura R., Deguchi Y., Yokogama K., Yamana T. Physiologically based pharmacokinetics of valproic acid in rabbits. Int. J. Pharm. 1985, 27:45-60.
12. Isoherranen N., White H.S., Klein B.D., Roeder M., Yagen B., Woodhead J.H., Schurig V., Bialer M. Pharmacokinetic-pharmacodynamic relationships of 2S,3S-valnoctamide and its stereoisomer 2R,3S-valnoctamide in animal models for epilepsy. Pharm. Res. 2003, 20:1293-1301.
13. Isoherranen N., White H.S., Finnell R.H., Yagen B., Woodhead J.H., Bennett G.D., Wilcox K.S., Barton M.E., Bialer M. Anticonvulsant profile and teratogenicity of N-methyl tetramethylcyclopropyl carboxamide: a new antiepileptic drug. Epilepsia 2002, 43:115-126.
14. Isoherranen N., Yagen B., Woodhead J.H., Spiegelstein O., Blotnik S., Wilcox K.S., Finnell R.H., Bennett G.D., White H.S., Bialer M. Characterization of the anticonvulsant pharmacokinetics of the chiral valporlamide propylisopropyl acetamide in rodents. Br. J. Pharmacol. 2003, 138:602-613.
15. Klein J., Koppen A., Leffelholz K. Uptake and storage of choline by rat-brain - influence of dietary choline supplementation. J. Neurochem. 1991, 57:370-375.
16. Klein J., Koppen A., Leffelholz K., Scmitthenner J. Uptake and metabolism of choline by rat-brain after acute choline administration. J. Neurochem. 1992, 58:870-876.
17. Lockard J.S., Viswanthan C.T., Levy R.H. Diurnal oscillations of CFS valproate in monkey. Life Sci. 1985, 36:1281-1285.
18. Loscher W. Animal models of epilepsy and epileptic seizures. Antiepileptic Drugs, Pharmacology and Therapeutics 1999, 19-62. Springer-Verlag, Berlin. M.J. Eadie, F.J.E. Vajda (Eds.).
19. Loscher W., Frey H. Kinetics of penetration of common antiepileptic drugs into cerebrospinal fluid. Epilepsia 1984, 25:346-352.
20. Loscher W., Nau H. Distribution of valproic acid and its metabolites in various brain areas of dogs and rats after acute and prolonged treatment. J. Pharmacol. Exp. Ther. 1983, 226:845-854.
21. Lothman E.W., Salerno R.A., Perlin J.B., Kaiser D.L. Screening and characterization of antiepileptic drugs with rapidly recurring hippocampal seizures in rats. Epilepsy Res. 1988, 2:366-379.
22. Pessah N., Bialer M., Wlodarczyk B., Finnell R.H., Yagen B. α-Fluoro-2,2,3,3-teteramethylcylcopropanecarboaxamide a novel potent anticonvulsant derivative of a cyclic analogue of valproic acid. J. Med. Chem. 2009, 52:2233-2242.
23. Racine R.J. Modification of seizure activity by electrical stimulation, II: motor seizure. Electroencephalogr. Clin. Neurophysiol. 1972, 32:281-294.
24. Shaltiel G., Shamir A., Shapiro J., Ding D., Dalton E., Bialer M., Harwood A.J., Belmaker R.H., Greenberg M.L., Agam G. Valpraote decreases inositol biosynthesis. Biol. Psychiatr. 2004, 56:868-874.
25. Shimshoni J.A., Bialer M., Wlodarczyk B., Finnell R., Yagen H.B. Potent anticonvulsant urea derivatives of constitutional isomers of valproic acid. J. Med. Chem. 2007, 50:6419-6427.
26. 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.
27. Sobol E., Yagen B., Lamb J.G., White H.S., Wlodarczyk B.J., Finnell R.H., Bialer M. Anticonvulsant activity, neural tube defect induction, mutagenicity and pharmacokinetics of a new potent antiepileptic drug, N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide. Epilepsy Res. 2007, 73:75-84.
28. White H., Steve, Woodhead J.H., Wlicox K.S., Stables J.P., Kupferberg H.J., Wolf H.N. General principles: discovery and preclinical development of antiepileptic drugs. Antiepileptic Drugs 2002, 36-48. Lippincott Williams and Wilkins, Philadelphia. 5th ed. R.H. Levy, R.H. Mattson, B.S. Meldrum, E. Perucca (Eds.).
29. Wieser H.G. Comparison of valproate concentrations in human plasma, CSF and brain distribution after administration of different formulations of valproate and valpromide. Epilepsy Res. 1991, 9:154-159.
30. Winkler I., Sobol E., Yagen B., Steinman A., Devor M., Bialer M. Efficacy of antiepileptic tetramethylcyclopropyl analogs of valproic acid amides in a rat model for neuropathic pain. Neuropharmacology 2005, 49:1110-1120.