The novel antiepileptic drug imepitoin compares favourably to other GABA-mimetic drugs in a seizure threshold model in mice and dogs

Pharmacological Research

Volumn 77, Issue , 2013, Pages 39-46

  Löscher, Wolfgang ^a,b   Hoffmann, Katrin ^a,d   Twele, Friederike ^a,b   Potschka, Heidrun ^c   Töllner, Kathrin ^a,b  

^a UNIVERSITY OF VETERINARY MEDICINE HANNOVER   (Germany)

^b CENTER FOR SYSTEMS NEUROSCIENCE   (Germany)

^c UNIVERSITY OF MUNICH   (Germany)

^d ABBOTT GMBH AND CO KG   (Germany)

Author keywords

Antiepileptic drugs; Benzodiazepine binding site; Epilepsy; GABA receptor; Imepitoin; Pentylenetetrazole

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ABECARNIL; CLONAZEPAM; DIAZEPAM; IMEPITOIN; PENTETRAZOLE; PHENOBARBITAL; VALPROIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR STIMULATING AGENT; ANTICONVULSIVE AGENT; CARBOLINE DERIVATIVE; IMIDAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICONVULSANT ACTIVITY; ARTICLE; CLONIC SEIZURE; CONTROLLED STUDY; DOG; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG POTENCY; DRUG TOLERABILITY; FEMALE; MALE; MOUSE; MYOCLONUS; NONHUMAN; PRIORITY JOURNAL; SEIZURE; SEIZURE THRESHOLD; AGONISTS; ANIMAL; BLOOD; CHEMICALLY INDUCED; COMPARATIVE STUDY; DOSE RESPONSE; PARTIAL AGONISM; SEIZURES;

ANIMALS; ANTICONVULSANTS; CARBOLINES; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG PARTIAL AGONISM; FEMALE; GABA-A RECEPTOR AGONISTS; IMIDAZOLES; MALE; MICE; PENTYLENETETRAZOLE; PHENOBARBITAL; SEIZURES;

EID: 84885112166     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2013.09.003     Document Type: Article

References (64)

1. M.C. Morganti-Kossmann, E. Yan, and N. Bye Animal models of traumatic brain injury: is there an optimal model to reproduce human brain injury in the laboratory? Injury 41 Suppl. 1 2010 S10 S13
2. K.L. Nowend, A.N. Starr-Moss, and K.E. Murphy The function of dog models in developing gene therapy strategies for human health Mamm Genome 22 2011 476 485
3. C. Zaragoza, C. Gomez-Guerrero, J.L. Martin-Ventura, L. Blanco-Colio, B. Lavin, and B. Mallavia Animal models of cardiovascular diseases J Biomed Biotechnol 2011 2011 497841
4. M.N. Bosch, M. Pugliese, J. Gimeno-Bayon, M.J. Rodriguez, and N. Mahy Dogs with cognitive dysfunction syndrome: a natural model of Alzheimer's disease Curr Alzheimer Res 9 2012 298 314
5. A.L. Dowling, and E. Head Antioxidants in the canine model of human aging Biochim Biophys Acta 1822 2012 685 689
6. K.A. Davis, B.K. Sturges, C.H. Vite, V. Ruedebusch, G. Worrell, and A.B. Gardner A novel implanted device to wirelessly record and analyze continuous intracranial canine EEG Epilepsy Res 96 2011 116 122
7. I.E. Leppik, E.N. Patterson, L.D. Coles, E.M. Craft, and J.C. Cloyd Canine status epilepticus: a translational platform for human therapeutic trials Epilepsia 52 Suppl. 8 2011 31 34
8. H. Potschka, A. Fischer, E.L. von Rüden, V. Hülsmeyer, and W. Baumgärtner Canine epilepsy as a translational model Epilepsia 54 2013 571 579
9. S. Steinmetz, A. Tipold, and W. Löscher Epilepsy after head injury in dogs: a natural model of posttraumatic epilepsy Epilepsia 54 2013 580 588
10. W. Löscher, and B.S. Meldrum Evaluation of anticonvulsant drugs in genetic animal models of epilepsy Fed Proc 43 1984 276 284 (Pubitemid 14185151)
11. W. Löscher, D. Schwartz-Porsche, H.-H. Frey, and D. Schmidt Evaluation of epileptic dogs as an animal model of human epilepsy Arzneim Forsch (Drug Res) 35 1985 82 87 (Pubitemid 15195785)
12. T.A. Holliday, J.G. Cunningham, and M.J. Gutnick Comparative clinical and electroencephalographic studies of canine epilepsy Epilepsia 11 1970 281 292
13. M. Podell Seizures in dogs Vet Clin North Am Small Anim Pract 26 1996 779 809 (Pubitemid 26233986)
14. M. Berendt, and L. Gram Epilepsy and seizure classification in 63 dogs: a reappraisal of veterinary epilepsy terminology J Vet Intern Med 13 1999 14 20
15. M. Berendt, H. Hogenhaven, A. Flagstad, and M. Dam Electroencephalography in dogs with epilepsy: similarities between human and canine findings Acta Neurol Scand 99 1999 276 283 (Pubitemid 29202184)
16. L. Kearsley-Fleet, D.G. O'Neill, H.A. Volk, D.B. Church, and D.C. Brodbelt Prevalence and risk factors for canine epilepsy of unknown origin in the UK Vet Rec 172 2013 338
17. K.R. Munana, D. Zhang, and E.E. Patterson Placebo effect in canine epilepsy trials J Vet Intern Med 24 2010 166 170
18. K.R. Munana, W.B. Thomas, K.D. Inzana, J.A. Nettifee-Osborne, K.J. McLucas, and N.J. Olby Evaluation of levetiracetam as adjunctive treatment for refractory canine epilepsy: a randomized, placebo-controlled, crossover trial J Vet Intern Med 26 2012 341 348
19. J. Venitz, and W. Sittner Appropriate dose selection - how to optimize clinical drug development 2007 Springer Berlin
20. P.R. Territo, K.J. Freise, K. Newhall, S.D. Barnhart, S.C. Peters, and D.R. Engleking Development and validation of the maximal electro-shock seizure model in dogs J Vet Pharmacol Ther 30 2007 508 515 (Pubitemid 350060563)
21. B.B. Gutsche, and C.R. Stephen Responses of dogs to hyperoxic-, pentylenetetrazol-, and electroshock-induced convulsions J Appl Physiol 22 1967 321 326
22. H.L. Edmonds Jr., S.I. Bellin, F.C. Chen, and G.A. Hegreberg Anticonvulsant properties of ropizine in epileptic and nonepileptic beagle dogs Epilepsia 19 1978 139 146 (Pubitemid 8328281)
23. P.R. Territo, H.E. Shannon, K. Newhall, S.D. Barnhart, S.C. Peters, and D.R. Engleking Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure model J Vet Pharmacol Ther 31 2008 562 570
24. D. Hasegawa, H. Orima, M. Fujita, K. Hashizume, and T. Tanaka Complex partial status epilepticus induced by a microinjection of kainic acid into unilateral amygdala in dogs and its brain damage Brain Res 955 2002 174 182 (Pubitemid 35284847)
25. R.P. Bircher, T. Kanait, and S.C. Wang Intravenous, cortical and intraventricular dose-effect relationship of pentylenetetrazol, picrotoxin and deslanoside in dogs Electroencephalogr Clin Neurophysiol 14 1962 256 267
26. W.W. Swingle, and A.J. Swingle Pentylenetetrazol (metrazol) shock in normal and adrenalectomized dogs Am J Physiol 205 1963 225 229
27. J. Zabara Inhibition of experimental seizures in canines by repetitive vagal stimulation Epilepsia 33 1992 1005 1012 (Pubitemid 23005257)
28. R. Neppl, C.M. Nguyen, W. Bowen, T. Al Saadi, J. Pallagi, and G. Morris In vivo detection of postictal perturbations of cerebral metabolism by use of proton MR spectroscopy: preliminary results in a canine model of prolonged generalized seizures Am J Neuroradiol 22 2001 1933 1943 (Pubitemid 33091965)
29. W. Löscher, H. Potschka, S. Rieck, A. Tipold, and C. Rundfeldt 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 45 2004 1228 1239 (Pubitemid 39350335)
30. W. Löscher Relationship between GABA concentrations in cerebrospinal fluid and seizure excitability J Neurochem 38 1982 293 295 (Pubitemid 12222496)
31. W. Löscher Alterations in CSF GABA levels and seizure susceptibility developing during repeated administration of pentetrazole in dogs. Effects of y-acetylenic GABA, valproic acid and phenobarbital Neurochem Int 5 1983 405 412 (Pubitemid 13048556)
32. W. Löscher, D. Hönack, R. Scherkl, A. Hashem, and H.-H. Frey 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 255 1990 541 548
33. W. Löscher Abecarnil shows reduced tolerance development and dependence potential in comparison to diazepam: animal studies D.N. Stephens, Anxiolytic β-carbolines: from molecular biology to the clinic 1993 Springer-Verlag Berlin 96 112
34. W. Löscher, D. Hönack, B. Nolting, and C.P. Faßbender Trans-2-en-valproate: reevaluation of its anticonvulsant efficacy in standardized seizure models in mice, rats and dogs Epilepsy Res 9 1991 195 210
35. M. Bialer, S.I. Johannessen, R.H. Levy, E. Perucca, T. Tomson, and H.S. White Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI) Epilepsy Res 103 2013 2 30
36. E. Sigel, R. Baur, R. Netzer, and C. Rundfeldt The antiepileptic drug AWD 131-138 stimulates different recombinant isoforms of the rat GABA(A) receptor through the benzodiazepine binding site Neurosci Lett 245 1998 85 88 (Pubitemid 28194889)
37. Z. Yasiry, and S.D. Shorvon How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years Epilepsia 53 Suppl. 8 2012 26 39
38. W. Löscher GABAmimetics in animal models of seizure states G. Bartholini, L. Bossi, K.G. Lloyd, P.L. Morselli, Epilepsy and GABA receptor agonists: basic and therapeutic research 1985 Raven Press New York 109 119
39. W. Löscher, D. Hönack, C.P. Fassbender, and B. Nolting The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs: III. Pentylenetetrazol seizure models Epilepsy Res 8 1991 171 189
40. D.N. Stephens, L. Turski, G.H. Jones, K.G. Steppuhn, and H.H. Schneider Abecarnil: a novel anxiolytic with mixed full agonist/partial agonist properties in animal models of anxiety and sedation D.N. Stephens, Anxiolytic β-carbolines 1993 Springer-Verlag Berlin 79 95
41. W. Löscher, and M.A. Rogawski How theories evolved concerning the mechanism of action of barbiturates Epilepsia 53 Suppl. 8 2012 12 25
42. W. Löscher The pharmacokinetics of antiepileptic drugs in rats: consequences for maintaining effective drug levels during prolonged drug administration in rat models of epilepsy Epilepsia 48 2007 1245 1258 (Pubitemid 47063087)
43. H. Potschka, M. Fedrowitz, and W. Löscher P-glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood-brain barrier: evidence from microdialysis experiments in rats Neurosci Lett 327 2002 173 176 (Pubitemid 34756625)
44. W. Löscher, and B. Nolting The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs: IV. Protective indices Epilepsy Res 9 1991 1 10
45. W. Löscher, B. Nolting, and C.P. Fassbender The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs: I. The influence of administration vehicles Epilepsy Res 7 1990 173 181
46. A. Rostock, C. Tober, R. Dost, C. Rundfeldt, C. Bartsch, and U. Egerland AWD-131-138 Drugs Future 23 1998 253 255 (Pubitemid 128719802)
47. P. Skolnick Anxioselective anxiolytics: on a quest for the Holy Grail Trends Pharmacol Sci 33 2012 611 620
48. E. Costa, and A. Guidotti Benzodiazepines on trial: a research strategy for their rehabilitation Trends Pharmacol Sci 17 1996 192 200 (Pubitemid 26186205)
49. A.K. Mehta, and M.K. Ticku An update on GABAA receptors Brain Res Brain Res Rev 29 1999 196 217
50. H. Möhler The rise of a new GABA pharmacology Neuropharmacology 60 2011 1042 1049
51. S. Yasar, J. Bergman, P. Munzar, G. Redhi, C. Tober, and N. Knebel Evaluation of the novel antiepileptic drug, AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys Eur J Pharmacol 465 2003 257 265 (Pubitemid 36397993)
52. H.-H. Frey Anticonvulsant drugs used in the treatment of epilepsy Probl Vet Med 1 1989 558 577
53. H.-H. Frey, and W. Löscher Pharmacokinetics of anti-epileptic drugs in the dog: a review J Vet Pharmacol Ther 8 1985 219 233
54. B.F.D. Bourgeois, W.E. Dodson, and J.A. Ferrendelli Primidone, phenobarbital and PEMA: I. Seizure protection, neurotoxicity and therapeutic index of individual compounds in mice Neurology 33 1983 283 290 (Pubitemid 13155757)
55. D.M. Boothe, C. Dewey, and D.M. Carpenter Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs J Am Vet Med Assoc 240 2012 1073 1083
56. D. Schwartz-Porsche, W. Löscher, and H.-H. Frey Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison J Vet Pharmacol Ther 8 1985 113 119
57. P.N. Patsalos, D.J. Berry, B.F. Bourgeois, J.C. Cloyd, T.A. Glauser, and S.I. Johannessen Antiepileptic drugs - best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies Epilepsia 49 2008 1239 1276 (Pubitemid 351991390)
58. W. Löscher, C. Rundfeldt, and D. Hönack Tolerance to anticonvulsant effects of the partial benzodiazepine receptor agonist abecarnil in kindled rats involves learning Eur J Pharmacol 202 1991 303 310
59. C. Rundfeldt, P. Wlaz, D. Hönack, and W. Löscher 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 275 1995 693 702 (Pubitemid 26023614)
60. W. Löscher, C. Rundfeldt, D. Hönack, and U. Ebert Long-term studies on anticonvulsant tolerance and withdrawal characteristics of benzodiazepine receptor ligands in different seizure models in mice: I. Comparison of diazepam, clonazepam, clobazam, and abecarnil J Pharmacol Exp Ther 279 1996 561 572
61. W. Löscher Preclinical assessment of proconvulsant drug activity and its relevance for predicting adverse events in humans Eur J Pharmacol 610 2009 1 11
62. W. Löscher, and D. Schmidt Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations Epilepsy Res 2 1988 145 181
63. S. Rieck, C. Rundfeldt, and A. Tipold Anticonvulsant activity and tolerance of ELB138 in dogs with epilepsy: a clinical pilot study Vet J 172 2006 86 95 (Pubitemid 43842917)
64. N. Shihab, J. Bowen, and H.A. Volk Behavioral changes in dogs associated with the development of idiopathic epilepsy Epilepsy Behav 21 2011 160 167