Antiepileptogenic effects of the novel synthetic neuroactive steroid, ganaxolone, against pentylenetetrazol-induced kindled seizures: Comparison with diazepam and valproate

Drug Development Research

Volumn 44, Issue 1, 1998, Pages 21-33

  Gasior, Maciej ^a,d,e,f   Beekman, Marjolein ^b   Carter, Richard B ^c   Goldberg, Steven R ^a   Witkin, Jeffrey M ^a  

^a NIDA Addiction Research Center   (United States)

^b UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^c Department of Pharmacokinetics and Drug Metabolism   (United States)

^d NIH Visiting Program

^e NATIONAL INSTITUTES OF HEALTH   (United States)

^f MEDICAL UNIVERSITY OF LUBLIN   (Poland)

Author keywords

Antiepileptic drugs; Convulsions; Epilepsy; Kindling; Locomotor activity; Neuroactive steroids

Indexed keywords

DIAZEPAM; GANAXOLONE; NEUROSTEROID; PENTETRAZOLE; VALPROIC ACID;

ANIMAL MODEL; ANTICONVULSANT ACTIVITY; ARTICLE; CLONIC SEIZURE; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFICACY; DRUG SAFETY; EPILEPSY; HUMAN; KINDLING; LETHALITY; MALE; MOUSE; SUBCUTANEOUS DRUG ADMINISTRATION; TONIC SEIZURE;

EID: 0031822330     PISSN: 02724391     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1098-2299(199805)44:1<21::AID-DDR4>3.0.CO;2-R     Document Type: Article

References (54)

1. Albertson TE, Joy RM, Stark LG (1984): A pharmacological study in the kindling model of epilepsy. Neuropharmacology 23:1117-1123.
2. Anderson WW, Swartzwelder HS, Wilson WA (1987): The NMDA receptor antagonist 2-amino-5-phosphonovalerate blocks stimulus train-induced epileptogenesis but not epileptiform bursting in the rat hippocampal slice. J Neurophysiol 57:1-21.
3. Beekman M, Ungard JT, Gasior M, Carter RB, Dijkstra D, Goldberg SR, Witkin JW (1998): Reversal of behavioral effects of pentylenetetrazol by the neuroactive steroid ganaxolone. J Pharmacol Exp Ther (in press).
4. Belelli D, Bolger MB, Gee KW (1989): Anticonvulsant profile of the progesterone metabolite 5 alpha-pregnan-3 alpha-ol-20-one. Eur J Pharmacol 166:325-329.
5. Belelli D, Lan NC, Gee KW (1990): Anticonvulsant steroids and the GABA/benzodiazepine receptor-chloride ionophore complex. Neurosci Biobehav Rev 14:315-322.
6. Bouma PA, Westendorp RG, van Dijk J, Peters AC, Brouwer OF (1996): The outcome of absence epilepsy: A meta-analysis. Neurology 47:802-808.
7. Bradford HF (1995): Glutamate, GABA and epilepsy. Prog Neurobiol 47:477-511.
8. Carter RB, Wood PL, Wieland S, Hawkinson JE, Belelli D, Lambert JJ, White HS, Wolf HH, Mirsadeghi S, Tahir SH, Bolger MB, Lan NC, Gee KW (1997): Characterization of the anticonvulsant properties of ganaxolone (CCD 1042; 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), a selective, high-affinity, steroid modulator of the gamma-aminobutyric acid(A) receptor. J Pharmacol Exp Ther 280:1284-1295.
9. Chapman A, Keane PE, Meldrum BS, Simiand J, Vernieres JC (1982): Mechanism of anticonvulsant action of valproate. Prog Neurobiol 19:315-359.
10. Croucher MJ, Bradford HF, Sunter DC, Watkins JC (1988): Inhibition of the development of electrical kindling of the prepiriform cortex by daily focal injections of excitatory amino acid antagonists. Eur J Pharmacol 152:29-38.
11. Croucher MJ, Cotterell KL, Bradford HF (1995): Amygdaloid kindling by repeated focal N-methyl-D-aspartate administration: Comparison with electrical kindling. Eur J Pharmacol 286:265-271.
12. De Deyn P, D'Hooge R, Marescau B, Pei YQ (1992): Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants. Epilepsy Res 12:87-110.
13. Dieterich E, Baier WK, Doose H, Tuxhorn I, Fichsel H (1985): Long-term follow-up of childhood epilepsy with absences. I. Epilepsy with absences at onset. Neuropediatrics 16:149-154.
14. Ferrendelli JA, Holland KD, McKeon AC, Covey DF (1989): Comparison of the anticonvulsant activities of ethosuximide, valproate, and a new anticonvulsant, thiobutyrolactone. Epilepsia 30:617-622.
15. Fisher RS (1989): Animal models of the epilepsies. Brain Res Brain Res Rev 14:245-278.
16. Gasior M, Carter RB, Goldberg SR, Witkin JM (1997): Anticonvulsant and behavioral effects of neuroactive steroids alone and in conjunction with diazepam. J Pharmacol Exp Ther 282:543-553.
17. Gee KW, Bolger MB, Brinton RE, Coirini H, McEwen BS (1988): Steroid modulation of the chloride ionophore in rat brain: Structure-activity requirements, regional dependence and mechanism of action. J Pharmacol Exp Ther 246:803-812.
18. A receptor complex: The pharmacological properties and therapeutic potential of epalons. Crit Rev Neurobiol 9:207-227.
19. Gilbert ME (1988): The NMDA-receptor antagonist, MK-801, suppresses limbic kindling and kindled seizures. Brain Res 463:90-99.
20. 35S-TBPS binding in the rat cerebral cortex induced by pentylenetetrazol kindling. Brain Res Bull 27:835-837.
21. Harrison NL, Simmonds MA (1984): Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res 323:287-292.
22. A receptor complex. J Pharmacol Exp Ther 241:346-353.
23. A receptor function. Mol Pharmacol 46:977-985.
24. Högskilde S, Wagner J, Carl P, Anker N, Angelo HR, Sörensen MB (1988): Anticonvulsive properties of pregnanolone emulsion compared with althesin and thiopentone in mice. Br J Anaesth 61:462-467.
25. ++ responses: Structure-activity studies. J Pharmacol Exp Ther 271:677-682.
26. Janz D (1985): Epilepsy: Seizures and syndromes. In Frey HH, Janz D (eds): Antiepileptic Drugs. Handbook of Experimental Pharmacology, Vol. 74. Berlin: Springer, pp 3-34.
27. Juul-Jansen P (1986): Epidemiology of intractable epilepsy. In Schmidt D, Morselli PL (eds): Intractable Epilepsy: Experimental and Clinical Aspects. New York: Raven Press, pp 5-11.
28. Kokate TG, Svensson BE, Rogawski MA (1994): Anticonvulsant activity of neurosteroids: Correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther 270:1223-1229.
29. A receptor function. Trends Pharmacol Sci 16:295-303.
30. Leander JD, Lawson RR, Omstein PL, Zimmerman DM (1988): N-methyl-D-aspartic acid-induced lethality in mice: Selective antagonism by phencyclidine-like drugs. Brain Res 448:115-120.
31. Leviel V, Naquet R (1977): A study of the action of valproic acid on the kindling effect. Epilepsia 18:229-234.
32. Litchfield JT, Wilcoxon F (1949): A simplified method of evaluating dose-effect experiments. J Pharm Exp Ther 95:99-113.
33. Loiseau P, Pestre M, Dartigues JE Commenges D, Barberger-Gateau C, Cohadon S (1983): Long-term prognosis in two forms of childhood epilepsy: Typical absence seizures and epilepsy with rolandic (centrotemporal) EEG foci. Ann Neurol 13:642-648.
34. Löscher W, Schmidt D (1988): Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res 2:145-181.
35. Löscher W, Schmidt D (1994): Strategies in antiepileptic drug development: Is rational drug design superior to random screening and structural variation? Epilepsy Res 17:95-134.
36. A receptor channels. Annu Rev Neurosci 17:569-602.
37. Majewska MD (1992): Neurosteroids: Endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog Neurobiol 38:379-395.
38. Mattson RH (1995): Selection of antiepileptic drugs therapy. In Levy RH, Mattson RH, Meldrum BS (eds): Antiepileptic Drugs, Fourth Edition. New York: Raven Press, pp 123-135.
39. McNamara JO (1989): Development of new pharmacological agents for epilepsy: Lessons from the kindling model. Epilepsia 30(Suppl 1):S13-S18.
40. McNamara JO, Bonhaus DW, Shin C (1993): The kindling model of epilepsy. In Schwartzkroin PA (ed): Epilepsy: Models, Mechanisms, and Concepts. Cambridge, UK: Cambridge University Press, pp 27-47.
41. Mody I, Stanton PK, Heinemann U (1988): Activation of N-methyl-D-aspartate receptors parallels changes in cellular and synaptic properties of dentate gyrus granule cells after kindling. J Neurophysiol 59:1033-1054.
42. A receptors. Neuron 4:759-765.
43. Racine R, Livingston K, Joaquin A (1975): Effects of procaine hydrochloride, diazepam, and diphenylhydantoin on seizure development in cortical and subcortical structures in rats. Electroencephalogr Clin Neurophysiol 38:355-365.
44. Rogawski MA, Porter RJ (1990): Antiepileptic drugs: Pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev 42:223-286.
45. Schwartzkroin PA, Prince DA (1980): Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res 183:61-76.
46. Shinnar S, Berg AT (1996): Does antiepileptic drug therapy prevent the development of "chronic" epilepsy? Epilepsia 37:701-708.
47. Silver JM, Shin C, McNamara JO (1991): Antiepileptogenic effects of conventional anticonvulsants in the kindling model of epilepsy. Ann Neurol 29:356-363.
48. Tallarida RJ, Murray RB (1987): Manual of Pharmacologic Calculations with Computer Programs. New York: Springer-Verlag.
49. Trimble MR (1996): Psychiatric disorders in epilepsy. In Shorvon S, Dreifuss F, Fish D, Thomas D (eds): The Treatment of Epilepsy. Oxford, UK: Blackwell Science, pp 337-344.
50. Vezzani A, Wu HQ, Moneta E, Samanin R (1988): Role of the N-methyl-D-aspartate-type receptors in the development and maintenance of hippocampal kindling in rats. Neurosci Lett 87:63-68.
51. Walker MC, Sander JW (1996): The impact of new antiepileptic drugs on the prognosis of epilepsy: Seizure freedom should be the ultimate goal. Neurology 46:912-914.
52. Weidenfeld J, Siegel RA, Chowers I (1980): In vitro conversion of pregnenolone to progesterone by discrete brain areas of the male rat. J Steroid Biochem 13:961-963.
53. White US, Woodhead JH, Franklin MR, Swinyard EA, Wolf HH (1995): Experimental selection, quantification, and evaluation of antiepileptic drugs. In Levy RH, Mattson RH, Meldrum BS (eds): Antiepileptic Drugs, Fourth Edition. New York: Raven Press, pp 99-110.
54. Wieland S, Belluzzi JD, Stein L, Lan NC (1995): Comparative behavioral characterization of the neuroactive steroids 3 alpha-OH,5 alpha-pregnan-20-one and 3 alpha-OH,5 beta-pregnan-20-one in rodents. Psychopharmacology (Berl) 118: 65-71.