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Effect of thioperamide, a histamine H3 receptor antagonist, on electrically induced convulsions in mice
H Yokoyama1, K Onodera, K Iinuma
1Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
The effect of thioperamide, a histamine H3 receptor antagonist, on electrically induced convulsions was studied in mice. Thioperamide significantly and dose dependently decreased the duration of each phase of convulsion and raised the electroconvulsive threshold. Its anticonvulsant effects were prevented by pretreatment with (R)-alpha-methylhistamine, a histamine H3 receptor agonist. These findings suggest that the effect of thioperamide on electrically induced convulsions is due to an increase in endogenous histamine release in the brain, an effect mediated by histamine H3 receptors. The anticonvulsant effect of thioperamide was antagonized strongly by mepyramine (or pyrilamine), a centrally acting histamine H1 receptor antagonist, but not by zolantidine, a centrally acting histamine H2 receptor antagonist. Thus, the blockade by mepyramine of the thioperamide-induced decrease in seizure susceptibility indicates that histamine released by thioperamide from the histaminergic nerve terminals interacts with the histamine H1 receptors of postsynaptic neurons. These findings support the hypothesis that the central histaminergic system is involved in the inhibition of seizures.
Insights
Thioperamide, a histamine H3 receptor antagonist, demonstrated anticonvulsant effects in mice by reducing seizure duration and increasing the seizure threshold. These effects are mediated by histamine H1 receptors, suggesting the central histaminergic system
Area of Science:
- Neuropharmacology
- Histamine receptor research
- Epilepsy research
Background:
- The role of the central histaminergic system in neurological disorders is increasingly recognized.
- Histamine receptors, particularly H1, H2, and H3 subtypes, are implicated in various brain functions.
- Histamine H3 receptor antagonists are being investigated for potential therapeutic applications.
Purpose of the Study:
- To investigate the anticonvulsant properties of thioperamide, a histamine H3 receptor antagonist.
- To elucidate the receptor mechanisms underlying the anticonvulsant effects of thioperamide.
- To explore the involvement of the central histaminergic system in seizure inhibition.
Main Methods:
- Electrically induced convulsions were utilized in a mouse model.
- Thioperamide was administered at varying doses to assess its effect on seizure parameters.
- Receptor agonists and antagonists (histamine H3 and H1/H2 receptor antagonists) were used to probe the mechanism of action.
Main Results:
- Thioperamide significantly and dose-dependently reduced the duration of seizure phases and elevated the electroconvulsive threshold.
- The anticonvulsant effects were reversed by a histamine H3 receptor agonist, (R)-alpha-methylhistamine.
- Histamine H1 receptor antagonist mepyramine, but not H2 antagonist zolantidine, blocked thioperamide's anticonvulsant action.
Conclusions:
- Thioperamide exhibits significant anticonvulsant effects mediated through the histamine H3 receptor.
- The observed effects are attributed to increased endogenous histamine release, acting on postsynaptic histamine H1 receptors.
- These findings support the hypothesis that the central histaminergic system plays a role in inhibiting seizures.