Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs

Fisher, Robert S.; Blum, David

doi:10.1111/j.1528-1157.1995.tb05993.x

Cited by 30 publications

(8 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other putative antiepileptic drugs are in phase 1 animal testing or in the process of moving from animal testing to patients, e.g. LO59 and losigamone [11]. The assess-ment of a potential role of each agent in treatment of schizophrenia will require clinical testing and studies in the future.…”

Section: Discussionmentioning

confidence: 99%

Antiepileptic drugs in schizophrenia: a review

Hosák

Libiger

2002

Eur. psychiatr.

View full text Add to dashboard Cite

The first choice group of psychotropic agents in schizophrenia is neuroleptics. However, this treatment is not effective in all patients and with every symptom. We summarize papers published on the role of antiepileptic drugs in treatment-resistant schizophrenia. We have searched the computer database system MEDLINE for relevant articles including reviews, reports of drug studies and case histories. Antiepileptic drugs can change symptoms of schizophrenia by their action on GABA-ergic neurotransmission or via anti-glutamatergic mechanisms. High doses of adjunctive benzodiazepines reduce positive symptoms, anxiety, and agitation. Carbamazepine is effective in affective symptoms of schizophrenia and influences violent behavior in psychotic patients. Its anti-kindling action may represent a promising treatment strategy for some patients with chronic course of schizophrenia. Valproate treatment leads to a decrease in positive symptoms as well as hostility. Lamotrigine is expected to influence the positive, negative, affective, and cognitive symptoms of schizophrenia. New antiepileptics (e.g., gabapentin, oxcarbazepine, topiramate, vigabatrin) present a promise as potential adjuncts to neuroleptic treatment in resistant symptoms of schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 99%

Antiepileptic drugs in schizophrenia: a review

Hosák

Libiger

2002

Eur. psychiatr.

View full text Add to dashboard Cite

show abstract

“…Therefore, a lack of agonist BZ-like efficacy is not the explanation for lack of ataxia. Likewise, the anticonvulsant loreclezole has ␤ 2/3 -subunit selectivity, diazepam-like efficacy, and anxiolytic/ anticonvulsant activity in animal models with reduced sedative effects (Smith et al, 2004;Groves et al, 2006) and is a nonsedating antiepileptic in human clinical trials (Fisher and Blum, 1995). Etifoxine, with ␤ 2/3 -subunit selectivity, also has diazepam-like efficacy at GABA A Rs (Smith et al, 2004) and is used clinically as a nonsedating anxiolytic (Nguyen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Limiting Activity at β1-Subunit-Containing GABAA Receptor Subtypes Reduces Ataxia

Gee¹,

Tran²,

Hogenkamp³

et al. 2010

The Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

GABA A receptor (R) positive allosteric modulators that selectively modulate GABA A Rs containing ␤ 2 -and/or ␤ 3 -over ␤ 1 -subunits have been reported across diverse chemotypes. Examples include loreclezole, mefenamic acid, tracazolate, and etifoxine. In general,"␤ 2/3 -selective" GABA A R positive allosteric modulators are nonbenzodiazepines (nonBZs), do not show ␣-subunit isoform selectivity, yet have anxiolytic efficacy with reduced ataxic/sedative effects in animal models and humans. Here, we report on an enantiomeric pair of nonBZ GABA A R positive allosteric modulators that demonstrate differential ␤-subunit isoform selectivity. We have tested this enantiomeric pair along with a series of other ␤ 2/3 -subunit selective, ␣-subunit isoform-selective, BZ and nonBZ GABA A positive allosteric modulators using electrophysiological, pharmacokinetic, and behavioral assays to test the hypothesis that ataxia may be correlated with the extent of modulation at ␤ 1 -subunit-containing GABA A Rs. Our findings provide an alternative strategy for designing anxioselective allosteric modulators of the GABA A R with BZ-like anxiolytic efficacy by reducing or eliminating activity at ␤ 1 -subunit-containing GABA A Rs.Positive allosteric modulators of the GABA A receptor (R) such as the benzodiazepines (BZs) continue to be used to treat anxiety, despite the well-known side effect of sedation. Diverse drug discovery efforts over two decades have focused on generating "anxioselective" (i.e., reducing anxiety without sedation) GABA A R positive allosteric modulators. Medicinal chemistry efforts have focused primarily on modifications of the BZ template with limited success in reducing sedative liability (Whiting, 2006).One strategy to generate anxioselective positive allosteric modulators involves creation of positive allosteric modulators that selectively modulate individual GABA A R subtypes involved in anxiety, while avoiding those mediating sedation. Several laboratories have focused on ␣-subunit isoform-selective BZ site agonists that evoke positive modulation of ␣ 2 -and ␣ 3 -but not ␣ 1 -subunit-containing GABA A Rs. This "␣ 2/3 -selective" approach is based on pharmacological and genetic data suggesting that ␣ 2 -and ␣ 3 -subunit-containing GABA A Rs mediate the anxiolytic actions of BZs, whereas those with ␣ 1 -subunits, especially the ␣ 1 ␤ 2 ␥ 2 subtype, are thought to mediate their sedative effects (Rudolph et al., 1999;McKernan et al., 2000). Consistent with this general theory, L-838,417 is a ␣ 2,3 -subunit-selective partial agonist BZ receptor ligand reported to be anxioselective in animal models (McKernan et al., 2000). However, recent clinical studies designed to determine whether ␣ 2,3 -subunit selectivity imparts reduced sedative liability has resulted in equivocal results where BZ-like side effects were observed (de Haas et al., 2008(de Haas et al., , 2009. Moreover, the ␣ 3 -subunit-selective BZ site partial agonist adipiplon has potent sedative activity and was in clinical development as a sedative...

show abstract

“…A greater therapeutic potential and lower incidence of side effects were described for 1,5-BZDs when compared to 1,4-BZDs. 1,5-BZD is used as adjuvant therapy in resistant cases of epilepsies [ 5 ]. BZDs exhibit potent anticonvulsant actions in a wide variety of animal seizures models.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticonvulsant Activity of Various Mannich and Schiff Bases of 1,5-Benzodiazepines

Pandeya

Rajput

2012

International Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Benzodiazepines have a various behavioral effects in addition to their anxiolytic action. There is every reason to believe that the BZ/GABA receptor complex is involved in these effects, since GABAmimetic manipulations modify the effect of BZ in tests of convulsive activity, motor function, and appetitive behavior. 1,5-Benzodiazepines are biologically important molecules and are extensively used clinically as analgesic, hypnotic, sedative, and antidepressive agents. Hence, 1,5-Benzodiazepines were synthesized by condensation of o-phenylenediamine and ketones, for example, cyclohexanone and acetone in presence of sulfated zirconia (catalyst). Mannich bases were synthesized with acetophenone, p-nitroacetophenone, p-chloroacetophenone, and formaldehyde. Schiff bases were synthesized using Mannich base of 1,5-benzodiazepines with p-chloroaniline and p-chlorophenylsemicarbazide in the presence of glacial acetic acid. All the synthesized compounds were characterized by 1H NMR and IR spectral analyses. All the synthesized derivatives were evaluated at the dose of 30 mg/kg b.w for anticonvulsant activity by isoniazid induced convulsion model, and the compounds NBZD-3 and NBZD-8 were found to be the most active among all compounds. Among all the synthesized derivatives, compounds NBZD-13 and NBZD-17 were found to be the most active among all compounds using thiosemicarbazide induced model. Although NBZD-8, NBZD-10, and NBZD-18 are the compounds which had shown good anticonvulsant activity and have an advantage over that, they were not sedative.

show abstract

Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs

Cited by 30 publications

References 86 publications

Antiepileptic drugs in schizophrenia: a review

Antiepileptic drugs in schizophrenia: a review

Limiting Activity at β1-Subunit-Containing GABAA Receptor Subtypes Reduces Ataxia

Synthesis and Anticonvulsant Activity of Various Mannich and Schiff Bases of 1,5-Benzodiazepines

Contact Info

Product

Resources

About