The effects of GABA receptor agonists and benzodiazepines on the minimal neurotoxicity and anticonvulsant activity of barbiturates in mice.

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Title The effects of GABA receptor agonists and benzodiazepines on the minimal neurotoxicity and anticonvulsant activity of barbiturates in mice.
Publication Type thesis
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Ulloque, Rafael Antonio
Date 1985-12
Description The effects of GABAa (progabide and THIP) or BABAb (baclofen) receptor agonists and benzodiazepines (diazepam and nitrazepam) on the minimal neurotoxicity and anticonvulsant activity of pentobarbital and phenobarbital in mice were investigated. When progabide, THIP, baclofen, diazepam, or nitrazepam was administered with pentobarbital the individual component (dose) of these drugs interacted additively by the individual component (dose) of these drugs interacted additively by the rotorod test. The administration of pentobarbital with progabide, diazepam or nitrazepam resulted in an additive effect by the pentylenetetrazol (PTZ) minimal threshold seizure (clonic) test. Likewise, combinations of phenobarbital with progabide, diazepam or nitrazepam produced an additive effect by the pentylenetetrazol (PTZ) test. THIP even after toxic doses did not alter the anti-PTZ activity of pentobarbital and phenobarbital. Combinations of pentobarbital with progabide, diazepam, or nitrazepam elicited an additive effect by the maximal electroshock seizure (MES) test. The administration of phenobarbital with progabide, diazepam, or nitrazepam resulted in an additive effect by the MES test THIP even after toxic doses did not alter the anti-MES activity of pentobarbital and phenobarbital. However, baclofen significantly potentiated the anti-MES activity of phenobarbital but not that of pentobarbital. These results suggest that a) in vitro interactions between barbiturates and either GABAa receptor agonists or benzodiazepines may not be the same in vivo, b) GABAa receptor may play a minor role in the minimal neurotoxicity and anticonvulsant activity of barbiturates, and c) inhibition of glutamate-induced excitation by baclofen may be an important action in potentiating the anti-MES activity of phenobarbital.
Type Text
Publisher University of Utah
Subject Drug Effects; Phenobarbital
Subject MESH Receptors, GABA-A; Barbiturates
Dissertation Institution University of Utah
Dissertation Name MS
Language eng
Relation is Version of Digital reproduction of "The effects of GABA receptor agonists and benzodiazepines on the minimal neurotoxicity and anticonvulsant activity of barbiturates in mice." Spencer S. Eccles Health Sciences Library. Print version of "The effects of GABA receptor agonists and benzodiazepines on the minimal neurotoxicity and anticonvulsant activity of barbiturates in mice." available at J. Willard Marriott Library Special Collection. RM 31.5 1985 U44.
Rights Management © Rafael Antonio Ulloque.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,20222
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship Fulbright/LASPAU institution.
ARK ark:/87278/s6v418t3
Setname ir_etd
ID 193486
Reference URL https://collections.lib.utah.edu/ark:/87278/s6v418t3
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