title: Evaluation of brain pharmacokinetics of (+)MK-801 in relation to behaviour.
abstract: The non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist (+)MK-801 is widely used in animal research (over 3000 publications), however its extracellular brain concentration has never been reported. Here, we show using in vivo microdialysis that systemic injection of (+)MK-801 at doses of 0.05, 0.1 or 0.2mg/kg resulted in peak brain ECF concentration of 6, 14 or 34 nM, respectively. Moreover, (+)MK-801 resulted in a dose-dependent learning impairment in the Morris water maze as well as hyperactivity in the open field. These data demonstrate for the first time that (+)MK-801 at doses producing behavioural alterations expected from NMDA receptor blockade reaches extracellular brain concentrations corresponding to the affinity at NMDA receptors.
authors.affiliation: Merz Pharmaceuticals GmbH, Dept. In vivo Pharmacology, Alfred-Wegener-Strasse 2, D-60438 Frankfurt am Main, Germany. nico.wegener@merz.de
authors.forename: Nico
authors.initials: N
authors.lastname: Wegener
authors.forename: Jens
authors.initials: J
authors.lastname: Nagel
authors.forename: Ralph
authors.initials: R
authors.lastname: Gross
authors.forename: Caroline
authors.initials: C
authors.lastname: Chambon
authors.forename: Sergio
authors.initials: S
authors.lastname: Greco
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Pietraszek
authors.forename: Andreas
authors.initials: A
authors.lastname: Gravius
authors.forename: Wojciech
authors.initials: W
authors.lastname: Danysz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017551:Microdialysis / Q000379:methods; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D018709:Statistics, Nonparametric
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate