Neurotoxicity of dipiperidinoethane due to in vivo conversion to a selective cholinesterase inhibitor.
Dipiperidinoethane (DPE) administration produces seizures and CNS lesions. Here we elucidate the cholinergic origin of DPE toxicity. DPE is both an acetylcholinesterase (AChE) inhibitor and a muscarinic antagonist. This dual action negates most of the toxic effects of the compound in vivo. The neurotoxicity is believed to arise from oxidative conversion to DPE-N-oxide, which selectively inhibits AChE. Cytotoxicity does not involve muscarinic neurons, since binding parameters were unchanged following in vivo exposure.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002540:Cerebral Cortex / Q000201:enzymology; D002800:Cholinesterase Inhibitors; D003292:Convulsants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D003292:Convulsants; D010880:Piperidines; D011976:Receptors, Muscarinic; C023791:dipiperidinoethane; C036080:dipiperidinoethane-di-N-oxide