title: Enhanced brain penetration of hexamethonium in complexes with derivatives of fullerene C60.
abstract: The present report describes development of hexamethonium complexes based on fullerene C60. Hexamethonium has a limited penetration into CNS and therefore can antagonize central effects of nicotine only when given at high doses. In the present studies conducted in laboratory rodents, intraperitoneal administration of hexamethonium-fullerene complexes blocked effects of nicotine (convulsions and locomotor stimulation). When compared to equimolar doses of hexamethonium, complexes of hexamethonium with derivatives of fullerene C60 were 40 times more potent indicating an enhanced ability to interact with central nicotine receptors. Thus, fullerene C60 derivatives should be explored further as potential carrier systems for polar drug delivery into CNS.
authors.affiliation: Institute of Experimental Medicine, St. Petersburg, Russia. levon-piotrovsky@yandex.ru.
authors.forename: L B
authors.initials: LB
authors.lastname: Piotrovskiy
authors.affiliation: Institute of Experimental Medicine, St. Petersburg, Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Litasova
authors.affiliation: Institute of Experimental Medicine, St. Petersburg, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Dumpis
authors.affiliation: Institute of Experimental Medicine, St. Petersburg, Russia.
authors.forename: D N
authors.initials: DN
authors.lastname: Nikolaev
authors.affiliation: Institute of Experimental Medicine, St. Petersburg, Russia.
authors.forename: E E
authors.initials: EE
authors.lastname: Yakovleva
authors.affiliation: Valdman Institute of Pharmacology, Pavlov First State Medical University of St. Petersburg, St. Petersburg, Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Dravolina
authors.affiliation: Valdman Institute of Pharmacology, Pavlov First State Medical University of St. Petersburg, St. Petersburg, Russia.
authors.forename: A Yu
authors.initials: AY
authors.lastname: Bespalov
mesh_terms: D000614:Aminocaproates / Q000737:chemistry; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D037741:Fullerenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006584:Hexamethonium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009538:Nicotine; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy
chemical_list: D000614:Aminocaproates; D000927:Anticonvulsants; D037741:Fullerenes; D006584:Hexamethonium Compounds; D018733:Nicotinic Antagonists; D009538:Nicotine; C069837:fullerene C60