Enhanced brain penetration of hexamethonium in complexes with derivatives of fullerene C60

Dokl Biochem Biophys. 2016 May;468(1):173-5. doi: 10.1134/S1607672916030030. Epub 2016 Jul 15.

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.

MeSH terms

  • Aminocaproates / chemistry
  • Animals
  • Anticonvulsants / chemistry
  • Anticonvulsants / pharmacokinetics
  • Brain / drug effects*
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Fullerenes / administration & dosage
  • Fullerenes / chemistry
  • Fullerenes / pharmacokinetics*
  • Hexamethonium Compounds / administration & dosage
  • Hexamethonium Compounds / chemistry
  • Hexamethonium Compounds / pharmacokinetics*
  • Locomotion / drug effects
  • Male
  • Mice
  • Nicotine
  • Nicotinic Antagonists / administration & dosage
  • Nicotinic Antagonists / chemistry
  • Nicotinic Antagonists / pharmacokinetics*
  • Rats, Wistar
  • Seizures / drug therapy

Substances

  • Aminocaproates
  • Anticonvulsants
  • Fullerenes
  • Hexamethonium Compounds
  • Nicotinic Antagonists
  • Nicotine
  • fullerene C60