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Effects of misoprostol on pentylenetetrazol-induced seizures in mice
C Medeiros F das1, M A Medeiros, V S Rao
1Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Brasil.
Abstract:
The effects of prostaglandin E-analogue misoprostol on the susceptibility to pentilenetetrazol (PTZ)-induced seizures were examined in mice. Misoprostol (200-800 micrograms/kg), given subcutaneously 45 min before the subconvulsive dose of PTZ (30 mg/kg, i.p) provoked dose-dependent clonic-tonic seizures (30 to 100%) and mortality in mice. At 300 g/kg, s.c., misoprostol pretreatment significantly (p < 0.05) lowered the onset latency to first convulsion as well as the latency to mortality induced by a convulsive dose of PTZ (60 mg/kg, i.p.). At this dose misoprostol was found to lower the CD50 and Ld50 values for PTZ by 21% and 36% respectively. The results suggest that prostaglandins are likely to lower the threshold for convulsions.
Insights
Prostaglandin E-analogue misoprostol increases susceptibility to pentylenetetrazol (PTZ)-induced seizures in mice. This suggests prostaglandins may lower the seizure threshold.
Area of Science:
- Neuroscience
- Pharmacology
- Convulsive Seizure Models
Background:
- Prostaglandins play a role in various physiological processes.
- The influence of prostaglandin E-analogue misoprostol on seizure susceptibility is not well understood.
Purpose of the Study:
- To investigate the effect of misoprostol on pentylenetetrazol (PTZ)-induced seizures in a mouse model.
- To determine if misoprostol alters the threshold for PTZ-induced convulsions.
Main Methods:
- Mice were pretreated with varying doses of misoprostol (200-800 µg/kg, s.c.) 45 minutes before PTZ administration.
- Subconvulsive (30 mg/kg, i.p.) and convulsive (60 mg/kg, i.p.) doses of PTZ were used to assess seizure induction and mortality.
- Seizure onset latency, mortality latency, CD50, and LD50 values were measured.
Main Results:
- Misoprostol administration (200-800 µg/kg) provoked dose-dependent clonic-tonic seizures and mortality.
- A dose of 300 µg/kg significantly reduced the latency to first convulsion and mortality.
- This dose also lowered the CD50 and LD50 for PTZ by 21% and 36%, respectively.
Conclusions:
- Prostaglandin E-analogue misoprostol enhances susceptibility to PTZ-induced seizures in mice.
- These findings suggest that prostaglandins may lower the threshold for seizure activity.