Mildronate exerts acute anticonvulsant and antihypnotic effects

Liga Zvejniece, Baiba Svalbe, Marina Makrecka, Edgars Liepinsh, Ivars Kalvinsh, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The effects of mildronate [3-(2,2,2-trimethylhydrazinium) propionate], an inhibitor of L-carnitine biosynthesis and an anti-ischaemic drug, were examined in various in-vivo conditions to investigate the neuropharmacological profile after acute administration. Mildronate (200(mg/kg, acute intraperitoneal administration) exerted anticonvulsant activity in a chemoconvulsant pentylenetetrazole-induced clonic and tonic seizure test but did not change the effects of a convulsion-inducing dose of (+)-bicuculline, a γ-aminobutyric acid receptor antagonist. Mildronate also dose-dependently inhibited the sleeping time in ethanol-induced loss of righting reflex test. However, in a pentylenetetrazole-induced seizure test, mildronate significantly stimulated the anticonvulsant activity of ethanol. The anticonvulsant activity of mildronate was completely blocked after pre-treatment with α2-adrenergic receptor antagonist yohimbine (2(mg/kg) and nitric oxide synthase inhibitor N-nitro-L-arginine (10(mg/kg). These results show that the acute administration of mildronate induces anticonvulsant and antihypnotic effects, which involve α2-adrenergic receptor and nitric oxide-dependent mechanisms. These findings indicate that the acute administration of mildronate could be beneficial for the treatment of seizures and alcohol intoxication.

Original languageEnglish
Pages (from-to)548-555
Number of pages8
JournalBehavioural Pharmacology
Volume21
Issue number5/6
DOIs
Publication statusPublished - Sep 2010
Externally publishedYes

Keywords

  • Anticonvulsant
  • cerebral blood flow
  • ethanol-induced loss of righting reflex
  • mildronate
  • mouse
  • oxygen saturation
  • pentylenetetrazole
  • rat

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

Fingerprint

Dive into the research topics of 'Mildronate exerts acute anticonvulsant and antihypnotic effects'. Together they form a unique fingerprint.

Cite this