Peripheral and central routes of administration of quaternary ammonium compound IEM-1460 are equally potent in reducing the severity of nicotine-induced seizures in mice.
Peripheral administration of nicotinic receptor antagonists with a quaternary ammonium group (hexamethonium and chlorisondamine) did not prevent the development of seizures induced by systemic treatment with nicotine in the toxic dose. The Me3N+ group with stable positive charge inhibits transport of these compounds into the brain through the blood-brain barrier. Intracerebral and peripheral (intraperitoneal) administration of compound IEM-1460 with the Me3N+ group was equally potent in reducing the severity of nicotine-induced seizures in mice. This phenomenon is related to the fact that IEM-1460 acts as a nicotinic receptor antagonist and polyamine agonist, which increases blood-brain barrier permeability for polar compounds. These features contribute to IEM-1460 transport into the brain. High anticonvulsant activity of IEM-1460 on the model of nicotine-induced seizures is associated with combined blockade of nicotinic receptors (alpha3beta4 receptors) and glutamate receptors (GluR1 AMPA receptors).
Gmiro
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Department of Neurophysiology, Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia. g2119@online.ru
Serdyuk
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Efremov
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OM
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001645:Biguanides / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy* / Q000401:mortality
D000218:Adamantane; D001645:Biguanides; D009538:Nicotine; D018091:Receptors, AMPA; D011978:Receptors, Nicotinic; C110702:IEM 1460; C403530:nicotinic receptor alpha3beta4; C006624:arcaine