Anticonvulsant profile of the imidazoquinazolines NNC 14-0185 and NNC 14-0189 in rats and mice

European Journal of Pharmacology

Volumn 308, Issue 1, 1996, Pages 21-30

  Jackson, Helen C ^a,d   Hansen, Holger C ^d   Kristiansen, Marit ^d   Suzdak, Peter D ^b,d   Klitgaard, Henrik ^c,d   Judge, Martin E ^d   Swedberg, Michael D B ^d  

^a ABBOTT LABORATORIES   (United States)

^b GUILFORD PHARMACEUTICALS INC   (United States)

^c UCB PHARMA   (Belgium)

^d NOVO NORDISK A S   (Denmark)

Author keywords

Benzodiazepine receptor; Epilepsy; NNC 14 0185; NNC 14 0189; Seizure threshold

Indexed keywords

3 (3 CYCLOPROPYL 5 ISOXAZOLYL) 6 FLUORO 5 MORPHOLINOIMIDAZO[1,5 A]QUINAZOLINE; 3 (5 CYCLOPROPYL 1,2,4 OXADIAZOL 3 YL) 7 FLUORO 5 (4 METHYL 1 PIPERAZINYL)IMIDAZO[1,5 A]QUINAZOLINE; ABECARNIL; BENZODIAZEPINE RECEPTOR; CLONAZEPAM; DIAZEPAM; FLUMAZENIL; IMIDAZOQUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTICONVULSANT THERAPY; ARTICLE; CONVULSION; DRUG EFFECT; EPILEPSY; INTRAPERITONEAL DRUG ADMINISTRATION; MALE; MOUSE; MUSCLE RELAXATION; NONHUMAN; PRIORITY JOURNAL; RAT; SEIZURE; SEIZURE THRESHOLD;

EID: 0030579858     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/0014-2999(96)00263-4     Document Type: Article

References (36)

1. De Deyn, P.P., R. D'Hooge, B. Marescau and Y.-Q. Pei, 1992, Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants, Epilepsy Res. 12, 87.
2. Gent. J.P., J.R.M. Haigh, A. Mehta and M. Feely, 1984, Studies on the nature of tolerance to the anticonvulsant effects of a 1,5-benzodiazepine, clobazam, in mice, Drugs Exp. Clin. Res. 10, 867.
3. Gent, J.P., M.P. Feely and J.R.M. Haigh, 1985, Differences between the tolerance characteristics of two anticonvulsant benzodiazepines. Life Sci. 37, 849.
4. Haefely, W. and P. Polc, 1986, Physiology of GABA enhancement by benzodiazepines and barbiturates, in: Benzodiazepine/GABA Receptors and Chloride Channels: Structural and Functional Properties, eds. R.W. Olsen and J.C. Venter (Alan R. Liss, New York) p. 97.
5. Haefely, W., M. Facklam, P. Schoch, J.R. Martin, E.P. Bonetti, J-L. Moreau, F. Jenck and J.G. Richards, 1992, Partial agonists of benzodiazepine receptors for the treatment of epilepsy, sleep, and anxiety disorders, in: GABAergic Synaptic Transmission, eds. G. Biggio, A. Concas and E. Costa (Raven Press, New York) p. 379.
6. Haigh, J.R.M. and M. Feely, 1988, Tolerance to the anticonvulsant effect of benzodiazepines. Trends Pharmacol. Sci. 9, 361.
7. Jackson, H.C. and D.J. Nutt, 1990, Body temperature discriminates between full and partial benzodiazepine receptor agonists, Eur. J. Pharmacol. 185, 243.
8. Jackson, H.C., H.C. Hansen, M. Kristiansen, P.D. Suzdak, M.E. Judge and M.D.B. Swedberg, 1995, Anticonvulsant effects of the imidazoquinazolines NNC 14-0185 and NNC 14-0189: comparison with diazepam, Br. J. Pharmacol. 114. 288P.
9. Jensen, L.H. and E.N. Petersen, 1983, Bidirectional effects of benzodiazepine receptor ligands against picrotoxin-and pentylenetetrazol-induced seizures, J. Neural Transm. 58, 183.
10. A receptor subtypes, J. Pharmacol. Exp. Ther. 266, 385.
11. Löscher, W., R. Jackel and S.J. Czuczwar. 1986, Is amygdala kindling in rats a model for drug-resistant partial epilepsy, Exp. Neurol. 93, 211.
12. Löscher, W., D. Honack, R. Scherkl, A. Hashem and H.-H. Frey, 1990. Pharmacokinetics, anticonvulsant efficacy and adverse effects of the beta-carboline abecarnil. a novel ligand for benzodiazepine receptors, after acute and chronic adminstration in dogs, J. Pharmacol, Exp. Ther. 255, 541.
13. Löscher, W., C. Rundfeldt and D. Honack. 1991, Tolerance to anticonvulsant effects of the partial benzodiazepine receptor agonist abecarnil in kindled rats involves learning. Eur. J. Pharmacol. 202, 303.
14. Macdonald, R.L. and J.L. Barker, 1978. Specific antagonism of GABA-mediated postsynaptic inhibition of cultured mammalian spinal cord neurons: a common mode of convulsant action, Neurology 28, 325.
15. Miller, L.G., W.R. Galpern, D.J. Greenblatt, M. Lumpkin and R.I. Shader, 1990, Chronic benzodiazepine administration. VI. A partial agonist produces behavioral effects without tolerance or receptor alterations, J. Pharmacol, Exp. Ther. 254, 33.
16. A-receptors: cell-specific expression, pharmacology, and regulation, Neurochem. Res. 20, 631.
17. Moreau, J,-L., F. Jenck, L. Pieri, P. Schoch, J.R. Martin and W.E. Haefely, 1990, Physical dependence induced in DBA/2J mice by benzodiazepine full agonists, but not by the partial agonist Ro 16-6028. Eur. J. Pharmacol. 190, 269.
18. Nutt, D.J., P.J. Cowen and H.J. Little, 1982, Unusual interactions of benzodiazepine receptor antagonists, Nature 295, 436.
19. Olsen, R.W., 1981. The GABA postsynaptic membrane receptor-ionophore complex. Site of action of convulsant and anticonvulsant drugs. Mol. Cell. Biochem. 39, 261.
20. Ozawa, M., Y. Nakada, K, Sugimachi, F. Yabuuchi, T. Akai, E. Mizuta, S. Kuno and M. Yamaguchi, 1994a, Pharmacological characterization of the novel anxiolytic beta-carboline abecarnil in rodents and primates, Jpn. J. Pharmacol. 64, 179.
21. Ozawa, M., K. Sugimachi, Y. Nakada-Kometani, T. Akai and M. Yamaguchi, 1994b, Chronic pharmacological activities of the novel anxiolytic beta-carboline abecarnil in rats, J. Pharmacol. Exp Ther. 269, 457.
22. A receptor subunits in the rat CNS, J. Comp. Neurol. 326, 193.
23. A receptor subtypes, in: Anxiolytic Beta-Carbolines: From Molecular Biology to the Clinic, ed, D.N. Stephens (Springer-Verlag, Berlin) p. 50.
24. Racine, R.J., 1972, Modification of seizure activity by electrical stimulation. II. Motor seizure, Electroencephalogr. Clin. Neurophysiol. 32, 281.
25. Rogawski, M.A. and R.J. Porter, 1990, Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds, Pharmacol. Rev. 42, 223.
26. Schmidt, D., W. Löscher and J. Oxley, 1986, Clinical development of benzodiazepines and other antiepileptic drugs for intractable epilepsy, in: Intractable Epilepsy, eds. D. Schmidt and P.L. Morselli (Raven Press, New York) p. 219.
27. Schneider, H.H., L. Turski, W. Krause and D.N. Stephens, 1990, Short- and long-term tolerance to abecarnil, a beta-carboline benzodiazepine-receptor ligand: antagonism of PTZ convulsion threshold vs. receptor occupation and plasma level in the mouse, Soc Neurosci. Abstr. 16, 1037.
28. A receptor family: molecular and functional diversity, Cold Spring Harbor Symposia on Quantitative Biology 55, 29.
29. A receptor function, in: Current Therapeutic Approaches to Pain and Other Anxiety Disorders Int. Acad. Biomed. Drug Res., eds, G. Darcourt, J. Mendlewicz, G. Racagni and N. Brunelli (Karger, Basel) Vol. 8, p. 90.
30. Stephens, D.N., H.H. Schneider, W. Kehr, J.S. Andrews, K.-J. Rettig, L. Turski, R. Schmiechen, J.D. Turner, L.H. Jensen, E.N. Petersen, T. Honore and J. Bondo Hansen, 1990, Abecarnil, a metabolically stable, anxioselective beta-carboline acting at henzodiazepine receptors, J. Pharmacol. Exp. Ther. 253, 334.
31. Stephens, D.N., L. Turski, M. Hillman, J.D. Turner, H.H. Scnneider and M. Yamaguchi, 1992, What are the differences between abecarnil and conventional benzodiazepine anxiolytics?, in: GABAergic Synaptic Transmission, eds. G. Biggio, A. Concas and E. Costa (Raven Press, New York) p. 395.
32. Steppuhn, K.G., 1992, The impact of excitatory amino acid transmission on withdrawal symptoms following chronic treatment of diazepam or the β-carboline, abecarnil. Doctoral thesis, Free University of Berlin.
33. Steppuhn, K.G., H.H. Schneider, L. Turski and D.N. Stephens, 1993, Long-term treatment with abecarnil does not induce diazepam-like dependence in mice, J. Pharmacol. Exp. Ther. 264, 1395.
34. Turski, L., D.N. Stephens, L.H. Jensen, E.N. Petersen, B.S. Meldrum, S. Patel, J. Bondo Hansen, W. Löscher, H.H. Schneider and R. Schmiechen, 1990, Anticonvulsant action of the be a-carboline abecarnil: studies in rodents and baboon, Papio papio, J. Pharmacol. Exp. Ther. 253, 344.
35. A receptor, Neuroreport 6, 1313.
36. A receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J. Neurosci. 3, 1040.