Antagonists of adenosine and alpha-2-adrenoceptors reverse the anticonvulsant effects of tizanidine in DBA/2 mice.
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.
De Sarro
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GB
Institute of Pharmacology, University of Reggio Calabria, Italy.
De Sarro
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A
D000241:Adenosine / Q000037:antagonists & inhibitors*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D010883:Piperoxan / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000927:Anticonvulsants; D000628:Aminophylline; D015016:Yohimbine; C023754:tizanidine; D010883:Piperoxan; D000241:Adenosine; D003000:Clonidine; D008784:Methysergide