title: Comparative study of taurine and tauropyrone: GABA receptor binding, mitochondrial processes and behaviour.
abstract: OBJECTIVE
  Taurine, a sulfur-containing amino acid, has high hydrophilicity and is poorly absorbed. Tauropyrone, a taurine-containing 1,4-dihydropyridine derivative, is suggested to have greater activity than taurine owing to improved physicochemical properties that facilitate delivery of the compound to target cells. The aim of this study was to determine whether the 1,4-dihydropyridine moiety in tauropyrone improves the pharmacological efficacy of taurine in vitro and in vivo.
  
  
  METHODS
  The effects of taurine and tauropyrone, as well as of the 1,4-dihydropyridine moiety were compared in in-vitro experiments to determine the binding to GABA receptors and influence on mitochondrial processes (isolated rat liver mitochondria), and in in-vivo tests to assess the influence on behavioural effects caused by the GABA-A receptor ligands, bicuculline, diazepam and ethanol.
  
  
  RESULTS
  Unlike taurine, tauropyrone did not display binding activity for the GABA-A receptor, and only taurine (but not tauropyrone) at low doses (0.1, 1.0 and 10 mg/kg) antagonised the bicuculline-induced convulsion effect. Taurine and tauropyrone had no effect on diazepam myorelaxing action, and they both exerted a comparable 'anti-ethanol' effect (shortening of the ethanol-sleeping time). Taurine and tauropyrone did not influence processes of mitochondrial bioenergetics.
  
  
  CONCLUSIONS
  The action of tauropyrone at the level of the GABA-A receptor differs qualitatively from that of taurine, probably because of its 1,4-dihydropyridine moiety, which may hinder access to the GABA-A receptor GABA site. Tauropyrone does not show improved pharmacological efficacy in in-vitro and in-vivo studies in comparison with taurine.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Latvia, 1A Sarlotes Street, Riga, Latvia. zanedz@e-apollo.lv
authors.forename: Zane
authors.initials: Z
authors.lastname: Dzirkale
authors.forename: Jolanta
authors.initials: J
authors.lastname: Pupure
authors.forename: Juris
authors.initials: J
authors.lastname: Rumaks
authors.forename: Simons
authors.initials: S
authors.lastname: Svirskis
authors.forename: Marija
authors.initials: M
authors.lastname: Vanina
authors.forename: Rudolfs
authors.initials: R
authors.lastname: Mezhapuke
authors.forename: Velga
authors.initials: V
authors.lastname: Sile
authors.forename: Maria Augusta
authors.initials: MA
authors.lastname: Fernandes
authors.forename: Gunars
authors.initials: G
authors.lastname: Duburs
authors.forename: Vija
authors.initials: V
authors.lastname: Klusa
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001640:Bicuculline / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D045442:Rotarod Performance Test / Q000379:methods; D012640:Seizures / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D004095:Dihydropyridines; D011963:Receptors, GABA-A; C518135:tauropyrone; D013654:Taurine; D000431:Ethanol; C038806:1,4-dihydropyridine; D003975:Diazepam; D001640:Bicuculline