title: Phenylephrine potentiates the anticonvulsant effect and neutralizes the sedative effect of diazepam in rats upon combined intragastric administration.
abstract: 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.
authors.affiliation: Research Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia.
authors.forename: S E
authors.initials: SE
authors.lastname: Serdyuk
authors.forename: V E
authors.initials: VE
authors.lastname: Gmiro
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003975:Diazepam / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004830:Epilepsy, Tonic-Clonic / Q000517:prevention & control*; D005753:Gastric Mucosa / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
chemical_list: D000927:Anticonvulsants; D004338:Drug Combinations; D006993:Hypnotics and Sedatives; D010656:Phenylephrine; D003975:Diazepam