Protection against soman-induced seizures in rats: relationship among doses of prophylactics, soman, and adjuncts.

Abstract

The combined effects of physostigmine and procyclidine (antagonizing muscarinic, nicotinic, and NMDA receptors) were tested against various doses of soman. Physostigmine (0.1 mg/kg) in combination with procyclidine doses of 1, 3, or 6 mg/kg effectively prevented the development of convulsions and hippocampally monitored seizures when the doses of soman were 1.3, 1.6, or 2 x LD50, respectively. Results from [(3)H]MK-801-binding experiments showed that procyclidine inhibits the phencyclidine site at the NMDA receptor in a concentration-dependent manner. Physostigmine (0.1 mg/kg) and procyclidine in a dose of 1 mg/kg did not prevent convulsions or seizures when the soman dose was 1.6 x LD50. Subsequent treatment with scopolamine in doses of 0.5 or 1 mg/kg immediately after (3 min) seizure onset showed that only the highest dose produced a reliable termination. When scopolamine (1 mg/kg) was given later (10 min) after onset of seizures, no effect was obtained. The sustained seizures were subsequently treated with diazepam (10 mg/kg) and pentobarbital (30 mg/kg) and finally terminated 25 min after onset. In rats given inadequate prophylaxis, both modified convulsions and seizures were seen. It is suggested that moderate doses of prophylactics should be preferred to avoid adverse effects on cognitive functions because insufficient prophylaxis can be compensated for by adjunct treatment.

• Authors: Trond Myhrer, Nga H T Nguyen, Jannike M Andersen, Pål Aas
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 196 Issue 3 Pg. 327-36 (May 01 2004) ISSN: 0041-008X [Print] United States
• PMID: 15094303 (Publication Type: Journal Article)

Chemical References

• Cholinesterase Inhibitors
• Convulsants
• Muscarinic Antagonists
• Neuroprotective Agents
• Dizocilpine Maleate
• Soman
• Physostigmine
• Procyclidine
• Scopolamine

Topics

• Animals
• Cholinesterase Inhibitors (administration & dosage, therapeutic use)
• Convulsants (administration & dosage, antagonists & inhibitors, toxicity)
• Dizocilpine Maleate (metabolism)
• Dose-Response Relationship, Drug
• Electroencephalography
• Hippocampus (drug effects, metabolism, pathology)
• Male
• Muscarinic Antagonists (therapeutic use)
• Neuroprotective Agents (metabolism)
• Physostigmine (therapeutic use)
• Procyclidine (therapeutic use)
• Rats
• Rats, Wistar
• Scopolamine (therapeutic use)
• Seizures (chemically induced, prevention & control)
• Soman (administration & dosage, antagonists & inhibitors, toxicity)