Epilepsy Research
Volume 23, Issue 3 , Pages 211-223 , April 1996

D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures

  • Angelika Rostock

      Affiliations

    • Department of Pharmacology, Corporate Research and Development, ASTA Medica Group, Arzneimittelwerk Dresden, Meissnerstr. 35, D-o1445 Radebeul, Germany
  • ,
  • Christine Tober

      Affiliations

    • Department of Pharmacology, Corporate Research and Development, ASTA Medica Group, Arzneimittelwerk Dresden, Meissnerstr. 35, D-o1445 Radebeul, Germany
  • ,
  • Chris Rundfeldt

      Affiliations

    • Corresponding Author InformationCorresponding author.
    • Department of Pharmacology, Corporate Research and Development, ASTA Medica Group, Arzneimittelwerk Dresden, Meissnerstr. 35, D-o1445 Radebeul, Germany
  • ,
  • Reni Bartsch

      Affiliations

    • Department of Pharmacology, Corporate Research and Development, ASTA Medica Group, Arzneimittelwerk Dresden, Meissnerstr. 35, D-o1445 Radebeul, Germany
  • ,
  • Jürgen Engel

      Affiliations

    • Department of Pharmacology, Corporate Research and Development, ASTA Medica Group, Arzneimittelwerk Dresden, Meissnerstr. 35, D-o1445 Radebeul, Germany
  • ,
  • Emanuele E. Polymeropoulos

      Affiliations

    • Department of Pharmacology, Corporate Research and Development, ASTA Medica Group, Arzneimittelwerk Dresden, Meissnerstr. 35, D-o1445 Radebeul, Germany
  • ,
  • Bernhard Kutscher

      Affiliations

    • Department of Pharmacology, Corporate Research and Development, ASTA Medica Group, Arzneimittelwerk Dresden, Meissnerstr. 35, D-o1445 Radebeul, Germany
  • ,
  • Wolfgang Löscher

      Affiliations

    • Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany
  • ,
  • Dagmar Hönack

      Affiliations

    • Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany
  • ,
  • H.Steve White

      Affiliations

    • Department of Pharmacology, University of Utah, Salt Lake City, Utah, USA
  • ,
  • Harold H. Wolf

      Affiliations

    • Department of Pharmacology, University of Utah, Salt Lake City, Utah, USA

Received 9 August 1995 ,Accepted 24 November 1995.

References 

  1. Dailey JW, Cheong JH, Ko KH, Adams-Curtis LE, Jobe PC. Anticonvulsant properties of D-20443 in genetically epilepsy-prone rats: prediction of clinical response. Neurosci. Lett. 1995;195:77–80
  2. Dam M. Intractable epilepsy: Introduction. In:  Schmidt D,  Morselli PL editor. Intractable Epilepsy: Experimental and Clinical Aspects. New York, NY: Raven Press; 1986;p. 1–3
  3. Dieter H-R, Engel J, Kutscher B, Polymeropoulos EE, Szelenyi S, Nickel B. Pharmaceutically active 1,2,4-triamino-benzene derivatives, processes of their preparation and pharmaceutical compositions containing them. 1995; United States Patent No. US0005,384,330
  4. Jakovlev V, Achterrath-Tuckermann U, von Schlichtegroll A, Strohman F, Thiemer K. Allgemeine pharmakologische Untersuchungen mit dem Analgetikum Flupirtin (General pharmacological studies with the analgesis flupirtine), Arzneim.-Forsch./Drug Res. 1985;35:44–55
  5. Kapetanovic IM, Yonekawa WD, Kupferberg HJ. The effects of anticonvulsant compounds on 4-aminopyridine-induced de novo synthesis of neurotransmitter amino acids in rat hippocampus in vitro. Epilepsy Res. 1995;20:113–120
  6. Kimball AW, Burnett WT, Doherty DG. Chemical protection against ionizing radiation. I. Sampling methods for screening compounds in radiation protection studies with mice. Radiat. Res. 1957;7:1–12
  7. Litchfield JT, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exp. Ther. 1949;96:99–113
  8. Loiseau P. Do we need novel anti-epileptic drugs?. Br. J. Clin. Pract. 1988;42:2–3
  9. Löscher W, von Hodenberg A, Nolting B, Fassbender C-P, Taylor C. Ralitoline: a reevaluation of anticonvulsant profile and determination of ‘active’ plasma concentrations in comparison with prototype antiepileptic drugs in mice. Epilepsia. 1991;32:560–568
  10. Löscher W, Nolting B. The role of technical, biological and pharmacological factors in the laboraory evaluation of anticonvulsant drugs. IV. Protective indices. Epilepsy Res. 1991;9:1–10
  11. Löscher W, Fassbender CP, Nolting B. The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seixure models. Epilepsy Res. 1991;8:79–94
  12. Löscher W, Hönack D, Fassbender CP, Nolting B. The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. III. Pentylenetetrazol seizure models. Epilepsy Res. 1991;8:171–189
  13. Nickel B, Shandra A, Godlevsky L, Mazarati A, Kupferberg H, Szelenyi I. Antiepileptic effects of a new drug: D-20443. Epilepsia. 1993;34(Suppl. 2):95
  14. Nickel B, Shandra A, Godlevsky L, Mazarati A, Kupferberg H, Szelenyi I. Anticonvulsant activity of D-20443. Naunyn-Schmiedenberg's Arch. Pharmacol. 1993;347:R142; (Suppl.)
  15. Polymeropoulos EE, Kutscher B. GABAergic activity of triamino-pyridines and triamino-benzenes. In:  Wermuth CG editors. Trends in QSAR and Molecular Modelling 92. Leiden: ESCOM; 1993;p. 456–460
  16. Rundfeldt C, Rohlfs A, Netzer R. Multiple actions of the new anticonvulsant D-23129 on voltage gated inward currents and GABA-induced currents in cultured neuronal cells. Naunyn Schmiedenberg's Arch. Pharmacol. 1995;351:R160; (Suppl.)
  17. Rundfeldt C, Tober C, Rostock A, Bartsch R. The phenylcarbamic acid ester D-23129 elevates potently the threshold for amygdala kindled seizures in rats at nontoxic doses. epilepsie-Blätter. 1994;7:29
  18. Rundfeldt, C., Wlaz, P., Hönack, D. and Löscher, W., Anticonvulsant tolerance and withdrawal characteristics of benzodiazepine receptor ligands in different seizure models in mice. Comparison of diazepam, bretazenil and abecarnil, J. Pharmacol. Exp. Ther. (in press).
  19. Sander JWAS, Shorvon SD. Incidence and prevalence studies in epilepsy and their methodological problems: a review. J. Neurol. Neurosurg. Psychiat. 1987;50:829–839
  20. Schmidt D. Anticonvulsants. In:  Duke MNG editors. Meyler's Side Effects of Drugs. 12th edition. Amsterdam: Elsevier; 1992;p. 122–143
  21. In:  Schmidt D,  Morselli PL editor. Intractable Epilepsy: Experimental and Clinical Aspects. New York, NY: Raven Press; 1986;
  22. Seaman CA, Sheridan PH, Engel J, Molliere M, Narang PK, Nice FJ. Flupirtine. In:  Meldrum BS,  Porter RJ editor. New Anticonvulsant Drugs. London: Libbey; 1986;p. 135–146
  23. Seydel JK, Schaper K-J, Coates EA, Cordes HP, Emig P, Engel J, et al. Synthesis and quantitative structure-activity relationship of anticonvulsant 2,3,6-triaminopyridines. J. Med. Chem. 1994;37:3016–3022
  24. Singh NA, Swinyard EE, White HS. Effects of prototype anticonvulsants on N-methyl-d-aspartate (NMDA)-induced seizures in mice. Fed. Am. Soc. Exp. Biol. J. 1988;2:A1068
  25. Swinyard EA. Laboratory evaluation of antiepileptic drugs. Review of laboratory methods. Epilepsia. 1969;10:107–119
  26. Swinyard EA, Brown WC, Goodman LS. Comparative assay of antiepileptic drugs in mice and rats. J. Pharmacol. Exp. Ther. 1952;106:319–330
  27. Swinyard EA, Wolf HH, White HS, Skeen GA, Stark LG, Albertson T, et al. Characterization of the anticonvulsant properties of F-721. Epilepsy Res. 1993;15:35–45
  28. Tober C, Jainta H, Rundfeldt C, Rostock A, Bartsch R. Anticonvulsant and antiepileptogenic effects of D-23129 in the kindling model of focal epilepsy. Naunyn-Schmiedeberg's Arch. Pharmacol. 1995;351:R160; (Suppl.)
  29. Tober, C., Rostock, A., Rundfeldt, C and Bartsch, R., D-23129: a potent anticonvulsant in the amygdala kindling model of complex partial seizures, Eur. J. Pharmacol. (in press).
  30. Tober C, Rundfeldt C, Rostock A, Bartsch R. The phenylcarbamic acid ester D-23129 is highly effective in epilepsy models for generalised and focal seizures at nontoxic doses. Soc. Neurosci. Abstr. 1994;20:1641
  31. Tober C, Rostock A, Bartsch R. The phenylcarbamic acid ester D-23129 is highly effective against amygdala kindled seizures in rats. Eur. J. Neurosci. 1994;(Suppl. 7):212
  32. White HS, Patel S, Meldrum BS. Anticonvulsant profile of MDL 27,266: an orally active, broad spectrum anticonvulsant agent. Epilepsy Res. 1992;12:217–226
  33. White HS, Wolf HH, Swinyard A, Skeen GA, Sofia RD. A neuropharmacological evaluation of felbamate as a novel anticonvulsant. Epilepsia. 1992;33:564–572
  34. Yonekawa WD, Kapetanovic IM, Kupferberg HJ. The effects of anticonvulsant agents on 4-aminopyridine induced epileptiform activity in rat hippocampus in vitro. Epilepsy Res. 1995;20:137–150

PII: 0920-1211(95)00101-8

Epilepsy Research
Volume 23, Issue 3 , Pages 211-223 , April 1996