1998
DOI: 10.1002/(sici)1098-2299(199805)44:1<21::aid-ddr4>3.0.co;2-r
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Antiepileptogenic effects of the novel synthetic neuroactive steroid, ganaxolone, against pentylenetetrazol-induced kindled seizures: Comparison with diazepam and valproate

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Cited by 16 publications
(27 citation statements)
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“…It was, however, ineffective against strychnine-and NMDA-evoked seizures although a clear-cut antilethal activity against NMDA was observed [112]. It is noteworthy that ganaxolone also inhibited pentylenetetrazol convulsions in fully kindled with pentylenetetrazol mice and its potency was even stronger than that of diazepam and valproate [113]. Only ganaxolone exhibited antiepileptogenic activity since it was capable of blocking the development of kindling -this effect was not shared by either diazepam or valproate [113].…”
Section: Profile Of Potential Antiepileptic Drugs Affecting Gaba-medimentioning
confidence: 96%
See 1 more Smart Citation
“…It was, however, ineffective against strychnine-and NMDA-evoked seizures although a clear-cut antilethal activity against NMDA was observed [112]. It is noteworthy that ganaxolone also inhibited pentylenetetrazol convulsions in fully kindled with pentylenetetrazol mice and its potency was even stronger than that of diazepam and valproate [113]. Only ganaxolone exhibited antiepileptogenic activity since it was capable of blocking the development of kindling -this effect was not shared by either diazepam or valproate [113].…”
Section: Profile Of Potential Antiepileptic Drugs Affecting Gaba-medimentioning
confidence: 96%
“…It is noteworthy that ganaxolone also inhibited pentylenetetrazol convulsions in fully kindled with pentylenetetrazol mice and its potency was even stronger than that of diazepam and valproate [113]. Only ganaxolone exhibited antiepileptogenic activity since it was capable of blocking the development of kindling -this effect was not shared by either diazepam or valproate [113]. Also, the neurosteroid was superior to the conventional antiepileptic drugs in terms of adverse activity since within the range of its anticonvulsant doses, ambulatory activity of mice was not disturbed [113].…”
Section: Profile Of Potential Antiepileptic Drugs Affecting Gaba-medimentioning
confidence: 98%
“…Neuroactive steroids have been shown to positively modulate the GABA A receptor function through a putative recognition site that is distinct from the benzodiazepine and barbiturate binding site [27]. The anticonvulsant property of neuroactive steroids has been reported [28][29][30]. Some neuroactive steroids such as allopregnalone (Fig.…”
Section: Othersmentioning
confidence: 99%
“…Interesting, the two rats that showed substitution in the present study were rats that did not press the diazepam-associated lever following pentobarbital administration, suggesting that pentobarbital and Co 2-1068 produced diazepam-like discriminative stimulus effects by different mechanisms. This hypothesis is also supported by research which shows that pentobarbital and diazepam do not share an identical pharmacological profile with neurosteroids such as Co 2-1068 (Gasior et al, 1998;Ungard et al, 2000). It is possible that testing higher doses of Co 2-1068 may have resulted in even greater substitution; however, insufficient drug supply prevented us from testing additional doses.…”
Section: Discussionmentioning
confidence: 86%
“…Evaluation of a number of site-selective NMDA antagonists was undertaken, including competitive NMDA antagonists (NPC 17742 and SDZ EAA 494;Ferkany et al, 1989;Lowe et al, 1990), an open channel blocker (PCP), glycine-site antagonists (ACEA 1021 and MDL 102,288;Kehne et al, 1995;Woodward et al, 1995), a polyamine-site antagonist and nitric oxide synthase inhibitor (arcaine; Kabuto et al, 1995;Reynolds, 1990), and a glutamate release inhibitor (riluzole; Doble, 1996). For comparison purposes, several drugs believed to affect GABAergic neurotransmission at GABA A receptors were also tested, including carbamazepine (an anticonvulsant), pentobarbital (a barbiturate), and Co 2-1068 (a neurosteroid; Gasior et al, 1998).…”
Section: Introductionmentioning
confidence: 99%