Antagonists of adenosine and alpha-2-adrenoceptors reverse the anticonvulsant effects of tizanidine in DBA/2 mice

Neuropharmacology. 1989 Mar;28(3):211-5. doi: 10.1016/0028-3908(89)90095-6.

Abstract

The anticonvulsant activity of 5-chloro-4-(2-imidazolin-2yl-amino)-2,1,3-benzothiazole, tizanidine, was studied following intraperitoneal (i.p.) administration in DBA/2 mice (which show sound-induced seizures). Protection against sound-induced seizures was observed after tizanidine, (0.5-4 mg/kg i.p.). The ED50 values for suppression of the tonic, clonic and wild running phases of sound-induced seizures were 0.54, 0.76 and 1.43 mg/kg, respectively. This protective action was significantly reduced by pretreatment with aminophylline (25 mg/kg i.p.), yohimbine (1 mg/kg i.p.) or piperoxan (20 mg/kg i.p.). Methysergide, a serotonin antagonists, did not significantly reduce the anticonvulsant effects of tizanidine. The present experiments suggest an involvement of purinergic and adrenergic mechanisms in the anticonvulsant action of tizanidine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / antagonists & inhibitors*
  • Adrenergic alpha-Antagonists / pharmacology*
  • Aminophylline / pharmacology
  • Animals
  • Anticonvulsants / antagonists & inhibitors*
  • Clonidine / analogs & derivatives*
  • Clonidine / antagonists & inhibitors
  • Habituation, Psychophysiologic / drug effects
  • Methysergide / pharmacology
  • Mice
  • Mice, Inbred DBA
  • Piperoxan / pharmacology
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-Antagonists
  • Anticonvulsants
  • Aminophylline
  • Yohimbine
  • tizanidine
  • Piperoxan
  • Adenosine
  • Clonidine
  • Methysergide