Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats.
Administration of pilocarpine or physostigmine to rats treated with lithium chloride produced sustained limbic seizures, widespread brain damage, and increased concentrations of D-myo-inositol-1-phosphate (a metabolite of the phosphoinositides, lipids involved in membrane receptor function) in the brain. The syndrome was preventable with atropine. The physostigmine doses and concentrations of blood lithium that caused the syndrome are similar to those considered appropriate for psychiatric chemotherapy.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002712:Chlorides / Q000009:adverse effects; D004347:Drug Interactions; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives / Q000032:analysis; D007295:Inositol Phosphates; D008094:Lithium / Q000009:adverse effects*; D018021:Lithium Chloride; D008297:Male; D010277:Parasympathomimetics / Q000009:adverse effects*; D010830:Physostigmine / Q000009:adverse effects; D010862:Pilocarpine / Q000009:adverse effects; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced*; D019966:Substance-Related Disorders / Q000209:etiology*
D002712:Chlorides; D007295:Inositol Phosphates; D010277:Parasympathomimetics; D010862:Pilocarpine; C002647:inositol 1-phosphate; D007294:Inositol; D001285:Atropine; D008094:Lithium; D010830:Physostigmine; D018021:Lithium Chloride