Benzodiazepine partially reverses tonic-clonic seizures induced by thiocolchicoside

Abstract

Seizures are a disorder caused by structural brain lesions, life-threatening metabolic derangements, or drug toxicity. The present study describes the behavior related to proconvulsant activity induced by thiocolchicoside (TCC) in rats and investigates the electrocorticographic patterns of this behavior and the effectiveness of classic antiepileptic drugs used to control these seizures. Forty-nine adult male Wistar rats were used and divided into two phases of our experimental design: 1) evaluation of seizure-related behavior and electrocorticographic patterns induced by TCC and 2) evaluation of the efficacy of classical antiepileptic drugs to control the proconvulsive activity caused by TCC. Our results showed that TCC induced tonicclonic seizures that caused changes in electrocorticographic readings, characteristic of convulsive activity, with average amplitude greater than that induced by pentylenetetrazole. Treatment with anticonvulsants, especially diazepam, reduced the electrocorticographic outbreaks induced by TCC. The results suggested that TCC caused seizures with increased power in brain oscillations up to 40 Hz and that diazepam may partially reverse the effects.

Epileptogenic activity of thiocolchicoside

“…used for decades as a valuable pharmacological model for the study of epileptic seizures. 8 Eventually, we also documented that the impermeability of the BBB to thiocolchicoside is likely to be related to the dose used and that the convulsant activity of this compound occurs mainly when there are minimal lesions of the BBB. 2,3 The relative impermeability of the BBB to therapeutic doses of thiocolchicoside may explain why very few case reports of thiocolchicoside-induced seizures in human patients have been reported in the literature, in spite of its extensive use in clinical practice for more than 40 years.…”

“…5,6 Interestingly, recent studies confirm the potent antagonistic effects of thiocolchicoside against GABA A Rs and its powerful epileptogenic activity. 7,8 Also, under specific experimental conditions, thiocolchicoside is more potent for the induction of seizures than pentylenetetrazol, a noncompetitive antagonist of the GABA A Rs, F I G U R E 1 Generalized electrographic seizure in a rat, with minimal lesions of dura and arachnoid membranes, 50 minutes after parenteral injection of thiocolchicoside, 6 mg/kg. L = left.…”