Assessment of the muscarinic receptor subtypes involved in pilocarpine-induced seizures in mice.

Abstract

We have used the pilocarpine-induced seizure model in mice and i.c.v. injection of subtype-specific receptor antagonists to investigate the muscarinic receptor subtype specificity of cholinergically-activated seizures. The rank order potencies of antagonists for inhibition of pilocarpine-induced seizures are atropine = telenzepine > 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMP) > pirenzepine with ID50's of 8.6, 12.0, 29.9, and 83.0 nmol/mouse, respectively. The M3-specific antagonists hexahydrosila-difenidol and its p-fluoro analog showed no effect on pilocarpine-induced seizures. The M2-specific antagonists gallamine and methoctramine cause seizures in mice in the absence of a pilocarpine injection. These seizures could be inhibited by coinjection of methoctramine with the M1-specific antagonist, pirenzepine. These data suggest a role of muscarinic M1 receptors in mediating pilocarpine-induced seizures and a role of the muscarinic M2 receptors in modulating neuronal activity.

• Authors: J A Maslanski, R Powelt, C Deirmengiant, J Patelt
• Journal: Neuroscience letters (Neurosci Lett) Vol. 168 Issue 1-2 Pg. 225-8 (Feb 28 1994) ISSN: 0304-3940 [Print] Ireland
• PMID: 8028781 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Parasympatholytics
• Piperidines
• Receptors, Muscarinic
• Pilocarpine
• telenzepine
• 4-fluorohexahydrosiladifenidol
• Pirenzepine
• Atropine
• 4-diphenylacetoxy-1,1-dimethylpiperidinium
• hexahydrosiladifenidol

Topics

• Animals
• Atropine (administration & dosage, pharmacology)
• Cerebral Ventricles (drug effects, physiology)
• Injections, Intraventricular
• Male
• Mice
• Parasympatholytics (pharmacology)
• Pilocarpine (administration & dosage, antagonists & inhibitors, toxicity)
• Piperidines (pharmacology)
• Pirenzepine (analogs & derivatives, pharmacology)
• Receptors, Muscarinic (classification, drug effects, physiology)
• Seizures (chemically induced, physiopathology)