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- Publisher Website: 10.1016/S0304-3940(02)00664-X
- Scopus: eid_2-s2.0-0037031571
- PMID: 12183024
- WOS: WOS:000178104400001
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Article: The benzodiazepine partial inverse agonist Ro15-4513 alters anticonvulsant and lethal effects of carbamazepine in amygdala-kindled rats
Title | The benzodiazepine partial inverse agonist Ro15-4513 alters anticonvulsant and lethal effects of carbamazepine in amygdala-kindled rats |
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Authors | |
Keywords | Amygdala kindling Anticonvulsant Benzodiazepine partial inverse agonist Carbamazepine Lethality Rat Ro15-4513 |
Issue Date | 2002 |
Publisher | Elsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neulet |
Citation | Neuroscience Letters, 2002, v. 329 n. 3, p. 253-256 How to Cite? |
Abstract | Ro15-4513 (ethyl-8-azido-5,6-dihydro-5methyl-6-oxo-4H-imidazo-[1,5-a]-1,4- benzodiazepine-3-carboxylate), a benzodiazepine partial inverse agonist of the GABAA receptor, is known to protect against alcohol toxicities. The present study was designed to determine the role of Ro15-4513 in preventing anticonvulsant, toxic, and lethal effects of carbamazepine (CBZ) in amygdala-kindled rats. Acute treatment with CBZ (25 mg/kg, i.p.) produced anticonvulsant effects in fully kindled rats characterized by a significant decrease in afterdischarge and seizure duration and stage. Repeated administration of this high dose of CBZ induced sedation and high (56%) lethality. The anticonvulsant and sedative effects of CBZ were strikingly suppressed by pretreatment with Ro15-4513 (2.5 and 5 mg/kg, i.p.), and there was no mortality in animals co-administrated with Ro15-4513 during the entire experimental period. These results indicate that Ro15-4513 protects against CBZ-induced sedation and lethality, while suppressing the anticonvulsant effects of CBZ, suggesting a role for the GABAA receptor in CBZ efficacy and side effects. The potential clinical implications for CBZ-induced toxicity and overdose remain to be explored. © 2002 Published by Elsevier Science Ireland Ltd. |
Persistent Identifier | http://hdl.handle.net/10722/179414 |
ISSN | 2023 Impact Factor: 2.5 2023 SCImago Journal Rankings: 0.745 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Zhang, ZJ | en_US |
dc.contributor.author | Postma, T | en_US |
dc.contributor.author | Obeng, K | en_US |
dc.contributor.author | Russell, S | en_US |
dc.contributor.author | Weiss, SRB | en_US |
dc.contributor.author | Post, RM | en_US |
dc.date.accessioned | 2012-12-19T09:56:17Z | - |
dc.date.available | 2012-12-19T09:56:17Z | - |
dc.date.issued | 2002 | en_US |
dc.identifier.citation | Neuroscience Letters, 2002, v. 329 n. 3, p. 253-256 | en_US |
dc.identifier.issn | 0304-3940 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/179414 | - |
dc.description.abstract | Ro15-4513 (ethyl-8-azido-5,6-dihydro-5methyl-6-oxo-4H-imidazo-[1,5-a]-1,4- benzodiazepine-3-carboxylate), a benzodiazepine partial inverse agonist of the GABAA receptor, is known to protect against alcohol toxicities. The present study was designed to determine the role of Ro15-4513 in preventing anticonvulsant, toxic, and lethal effects of carbamazepine (CBZ) in amygdala-kindled rats. Acute treatment with CBZ (25 mg/kg, i.p.) produced anticonvulsant effects in fully kindled rats characterized by a significant decrease in afterdischarge and seizure duration and stage. Repeated administration of this high dose of CBZ induced sedation and high (56%) lethality. The anticonvulsant and sedative effects of CBZ were strikingly suppressed by pretreatment with Ro15-4513 (2.5 and 5 mg/kg, i.p.), and there was no mortality in animals co-administrated with Ro15-4513 during the entire experimental period. These results indicate that Ro15-4513 protects against CBZ-induced sedation and lethality, while suppressing the anticonvulsant effects of CBZ, suggesting a role for the GABAA receptor in CBZ efficacy and side effects. The potential clinical implications for CBZ-induced toxicity and overdose remain to be explored. © 2002 Published by Elsevier Science Ireland Ltd. | en_US |
dc.language | eng | en_US |
dc.publisher | Elsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neulet | en_US |
dc.relation.ispartof | Neuroscience Letters | en_US |
dc.subject | Amygdala kindling | - |
dc.subject | Anticonvulsant | - |
dc.subject | Benzodiazepine partial inverse agonist | - |
dc.subject | Carbamazepine | - |
dc.subject | Lethality | - |
dc.subject | Rat | - |
dc.subject | Ro15-4513 | - |
dc.subject.mesh | Affinity Labels - Pharmacology | en_US |
dc.subject.mesh | Amygdala - Physiology | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Anticonvulsants - Toxicity | en_US |
dc.subject.mesh | Azides - Pharmacology | en_US |
dc.subject.mesh | Benzodiazepines - Pharmacology | en_US |
dc.subject.mesh | Carbamazepine - Toxicity | en_US |
dc.subject.mesh | Drug Interactions | en_US |
dc.subject.mesh | Epilepsy - Drug Therapy - Mortality - Physiopathology | en_US |
dc.subject.mesh | Gaba-A Receptor Agonists | en_US |
dc.subject.mesh | Kindling, Neurologic - Drug Effects | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Rats | en_US |
dc.subject.mesh | Rats, Sprague-Dawley | en_US |
dc.title | The benzodiazepine partial inverse agonist Ro15-4513 alters anticonvulsant and lethal effects of carbamazepine in amygdala-kindled rats | en_US |
dc.type | Article | en_US |
dc.identifier.email | Zhang, ZJ: zhangzj@hkucc.hku.hk | en_US |
dc.identifier.authority | Zhang, ZJ=rp01297 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1016/S0304-3940(02)00664-X | en_US |
dc.identifier.pmid | 12183024 | - |
dc.identifier.scopus | eid_2-s2.0-0037031571 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0037031571&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 329 | en_US |
dc.identifier.issue | 3 | en_US |
dc.identifier.spage | 253 | en_US |
dc.identifier.epage | 256 | en_US |
dc.identifier.isi | WOS:000178104400001 | - |
dc.publisher.place | Ireland | en_US |
dc.identifier.scopusauthorid | Zhang, ZJ=8061473900 | en_US |
dc.identifier.scopusauthorid | Postma, T=7003610812 | en_US |
dc.identifier.scopusauthorid | Obeng, K=6701594477 | en_US |
dc.identifier.scopusauthorid | Russell, S=7401538133 | en_US |
dc.identifier.scopusauthorid | Weiss, SRB=35448419700 | en_US |
dc.identifier.scopusauthorid | Post, RM=7202218145 | en_US |
dc.identifier.issnl | 0304-3940 | - |