Phenylephrine Potentiates the Anticonvulsant Effect and Neutralizes the Sedative Effect of Diazepam in Rats upon Combined Intragastric Administration

High doses of phenylephrine and diazepam (1 and 10 mg/kg, respectively) suppressed the development of generalized tonic-clonic pentylenetetrazole-induced convulsions in 86-100% rats, but did not prevent local clonic pentylenetetrazole-induced convulsions. Diazepam in the specified dose produced stro...

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Bibliographic Details
Published in:Bulletin of experimental biology and medicine 2014-12, Vol.158 (2), p.234-237
Main Authors: Serdyuk, S. E., Gmiro, V. E.
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants - administration & dosage
Anticonvulsants - pharmacology
Biomedical and Life Sciences
Biomedicine
Cell Biology
Diazepam
Diazepam - administration & dosage
Diazepam - antagonists & inhibitors
Diazepam - pharmacology
Dose-Response Relationship, Drug
Drug Combinations
Drug Evaluation, Preclinical
Drug Synergism
Epilepsy, Tonic-Clonic - prevention & control
Gastric Mucosa - drug effects
Hypnotics and Sedatives - administration & dosage
Hypnotics and Sedatives - antagonists & inhibitors
Hypnotics and Sedatives - pharmacology
Internal Medicine
Laboratory Medicine
Male
Pathology
Phenylephrine
Phenylephrine - administration & dosage
Phenylephrine - pharmacology
Rats
Rats, Wistar
Statistics, Nonparametric
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Summary:High doses of phenylephrine and diazepam (1 and 10 mg/kg, respectively) suppressed the development of generalized tonic-clonic pentylenetetrazole-induced convulsions in 86-100% rats, but did not prevent local clonic pentylenetetrazole-induced convulsions. Diazepam in the specified dose produced strong sedation, while phenylephrine had no sedative effect in the open-field test. Combined intragastric administration of phenylephrine in a medium and individually ineffective dose (0.3 mg/kg) and diazepam in a high dose (10 mg/kg) potentiated the anticonvulsant effect of diazepam: it prevented not only tonic-clonic, but also clonic pentylenetetrazole-induced convulsions in 100% rats and 2.6-fold increased anticonvulsant activity of diazepam. The specified combination of diazepam and phenylephrine had no sedative effect. The mechanism of potentiation of the anticonvulsive effect and elimination of the sedative side effect is based on stimulation of gastric mucosa afferents by phenylephrine.
ISSN:0007-4888
1573-8221
DOI:10.1007/s10517-014-2730-7