Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures

Epilepsia

Volumn 45, Issue 10, 2004, Pages 1228-1239

  Löscher, Wolfgang ^a   Potschka, Heidrun ^a   Rieck, Susanne ^a   Tipold, Andrea ^a   Rundfeldt, Chris ^b  

^a UNIVERSITY OF VETERINARY MEDICINE HANNOVER   (Germany)

^b Elbion AG   (Germany)

Author keywords

Antiepileptic drugs; Benzodiazepines; Epilepsy; GABA receptors

Indexed keywords

1 (4 CHLOROPHENYL) 4 MORPHOLINOIMIDAZOLIN 2 ONE; 4 AMINOBUTYRIC ACID RECEPTOR; 5 ISOPROPOXY 4 METHYL BETA CARBOLINE 3 CARBOXYLIC ACID ETHYL ESTER; BENZODIAZEPINE RECEPTOR BLOCKING AGENT; BENZODIAZEPINE RECEPTOR STIMULATING AGENT; FLUMAZENIL; IMIDAZOLINE DERIVATIVE; PENTETRAZOLE; PHENOBARBITAL; PRIMIDONE; UNCLASSIFIED DRUG; VALPROIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICONVULSANT ACTIVITY; ARTICLE; ATAXIA; BULIMIA; CHEMICAL ANALYSIS; CONTROLLED STUDY; DISEASE COURSE; DOG; DOSE RESPONSE; DRUG DEPENDENCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG TOLERABILITY; FEMALE; MALE; MONOTHERAPY; NONHUMAN; PRIORITY JOURNAL; RECURRENT DISEASE; SEIZURE; SEIZURE THRESHOLD;

ANIMALS; ANTICONVULSANTS; BROMIDES; CHRONIC DISEASE; DISEASE MODELS, ANIMAL; DOG DISEASES; DOGS; DRUG THERAPY, COMBINATION; EPILEPSY; FLUMAZENIL; GABA AGONISTS; IMIDAZOLES; PENTYLENETETRAZOLE; PHENOBARBITAL; POTASSIUM COMPOUNDS; PRIMIDONE; RECEPTORS, GABA-A; SEIZURES; SUBSTANCE WITHDRAWAL SYNDROME; TREATMENT OUTCOME;

EID: 5344234533     PISSN: 00139580     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.0013-9580.2004.21204.x     Document Type: Article

References (32)

1. Rostock A, Tober C, Dost R, et al. AWD-131-138: AWD-131-8. Drugs Fut 1998;23:253-5.
2. Bialer M, Johannessen SI, Kupferberg HJ, et al. Progress report on new antiepileptic drugs: a summary of the fourth Eilat conference (EILAT IV). Epilepsy Res 1999;34:1-41.
3. Bialer M, Johannessen SI, Kupferberg HJ, et al. Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V). Epilepsy Res 2001;43:11-58.
4. Sigel E, Baur R, Netzer R, et al. The antiepileptic drug AWD 131-138 stimulates different recombinant isoforms of the rat GABA(A) receptor through the benzodiazepine binding site. Neurosci Lett 1998;245:85-8.
5. Woods JH, Katz JL, Winger G. Abuse liability of benzodiazepines. Pharmacol Rev 1987;39:251-413.
6. Michelini S, Cassano GB, Frare F, et al. Long-term use of benzodiazepines: tolerance, dependence and clinical problems in anxiety and mood disorders. Pharmacopsychiatry 1996;29:127-34.
7. Bateson AN. Basic pharmacologic mechanisms involved in benzodiazepine tolerance and withdrawal. Curr Pharm Des 2002;8:5-21.
8. Costa E, Guidotti A. Benzodiazepines on trial: a research strategy for their rehabilitation. Trends Pharmacol Sci 1996;17:192-200.
9. Costa E. From GABA receptor diversity emerges a unified vision of GABAergic inhibition. Annu Rev Pharmacol Toxicol 1998;38:321-50.
10. A receptors. Brain Res Brain Res Rev 1999;29:196-217.
11. Yasar S, Bergman J, Munzar P et al. Evaluation of the novel antiepileptic drug, AWD 131-8, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys. Eur J Pharmacol 2003;465:257-65.
12. Löscher W, Hönack D, Faßbender CP. Physical dependence on diazepam in the dog: precipitation of different abstinence syndromes by the benzodiazepine receptor antagonists Ro 15-1788 and ZK 93426. Br J Pharmacol 1989;97:843-52.
13. Löscher W, Hönack D, Scherkl R, et al. Pharmacokinetics, anticonvulsant efficacy and adverse effects of the β-carboline abecarnil, a novel ligand for benzodiazepine receptors, after acute and chronic administration in dogs. J Pharmacol Exp Ther 1990;255:541-8.
14. Löscher W, Hönack D. Withdrawal precipitation by benzodiazepine receptor antagonists in dogs chronically treated with diazepam or the novel anxiolytic and anticonvulsant β-carboline abecarnil. Naunyn Schmiedebergs Arch Pharmacol 1992;345:452-60.
15. Frey H-H, Löscher W. Pharmacokinetics of anti-epileptic drugs in the dog: a review. J Vet Pharmacol Ther 1985;8:219-33.
16. Löscher W, Schwartz-Porsche D, Frey H-H, et al. Evaluation of epileptic dogs as an animal model of human epilepsy. Arzneimittelforschung (Drug Res) 1985;35:82-7.
17. Schwartz-Porsche D, Löscher W, Frey H-H. Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. J Vet Pharmacol Ther 1985;8:113-9.
18. Löscher W. Animal models of intractable epilepsy. Prog Neurobiol 1997;53:239-58.
19. Podell M. Antiepileptic drug therapy. Clin Tech Small Anim Pract 1998;13:185-92.
20. Löscher W, Hönack D, Nolting B, et al. Trans-2-en-valproate: Reevaluation of its anticonvulsant efficacy in standardized seizure models in mice, rats and dogs. Epilepsy Res 1991;9:195-210.
21. Martin WR, Sloan JW, Wala E. Precipitated abstinence in orally dosed benzodiazepine-dependent dogs. J Pharmacol Exp Ther 1990;255:744-55.
22. Frey HH, Philippin HP, Scheuler W. Development of tolerance to the anticonvulsant effect of diazepam in dogs. Eur J Pharmacol 1984;104:27-38.
23. Scherkl R, Scheuler W, Frey H-H. Anticonvulsant effect of clonazepam in the dog: development of tolerance and physical dependence. Arch Int Pharmacodyn Ther 1985;278:249-60.
24. Scherkl R, Kurudi D, Frey H-H. Clorazepate in dogs: tolerance to the anticonvulsant effect and signs of physical dependence. Epilepsy Res 1989;3:144-50.
25. Schneider S. AWD 131-8: 13-week oral toxicity study after repeated administration in beagle dogs and subsequent 6-week recovery period. ASTA Medica AG 2001; Study report no. A-04101/3000917357.
26. Hutchinson MA, Smith PF, Darlington CL. The behavioural and neuronal effects of the chronic administration of benzodiazepine anxiolytic and hypnotic drugs. Prog Neurobiol 1996;49:73-97.
27. Schoch P, Moreau JL, Martin JR, et al. Aspects of benzodiazepine receptor structure and function with relevance to drug tolerance and dependence. Biochem Soc Symp 1993;59:121-34.
28. Atack JR. Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. Curr Drug Target CNS Neurol Disord 2003;2:213-32.
29. Löscher W, Rundfeldt C. Intermittent flumazenil and benzodiazepine tolerance: discouraging findings in rats. Lancet 1989;1:1386-7.
30. Löscher W, Rundfeldt C. Development of tolerance to clobazam in fully kindled rats: effects of intermittent flumazenil administration. Eur J Pharmacol 1990;180:255-71.
31. Rogawski MA. Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents: toward an understanding of their favorable tolerability. Amino Acids 2000;19:133-49.
32. Löscher W. Pharmakologische Grundlagen zur Behandlung der Epilepsie bei Hund und Katze. Prakt Tierarzt 2003;84:574-86.