title: The effect of 7-fluoro-marsanidine, a novel α2-adrenoceptor agonist, on extracellular noradrenaline in rat frontal cortex: a microdialysis study.
abstract: Previous in vitro binding studies identified a 7-fluoro derivative of marsanidine, a partial α2-adrenoceptor (α2-AR) agonist, to display high affinity and selectivity for α2-AR over α1-AR, imidazoline-1 and imidazoline-2 binding sites. In the present study 7-fluoro-marsanidine is further characterised in vivo to investigate its pharmacological effects on extracellular noradrenaline (NA) levels at frontal cortex in conscious freely moving rats using the technique of in vivo brain microdialysis. Peripheral administration of 7-fluoro-marsanidine via intraperitoneal (i.p.) route at the dose of 0.1mg/kg slightly, but non-significantly, decreased extracellular NA level (maximum by 17% at 20 min) in rat frontal cortex compared to basal level. At a higher dose of 1mg/kg, 7-fluoro-marsanidine reduced cortical NA level (maximum by 73% at 40 min) significantly as compared to basal level between 20 and 80 min. In addition, systemic administration of 7-fluoro-marsanidine at both the doses produced rapid onset of sedation in rats. These data suggest that 7-fluoro-marsanidine is able to cross the blood-brain barrier and, by acting as an α2-AR agonist, reduces extracellular NA levels in rat frontal cortex in a dose related manner. Thus, initial studies indicate 7-fluoro-marsanidine to possess favourable functional properties at α2-AR.
authors: Department of Pharmacology, 9-47 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors: Mehnaz
authors: M
authors: Ferdousi
authors: Department of Pharmacology, 9-47 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors: Maggie
authors: M
authors: Lalies
authors: Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors: Aleksandra
authors: A
authors: Wasilewska
authors: Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors: Franciszek
authors: F
authors: Sączewski
authors: Department of Pharmacology, 9-47 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. Electronic address: alh2@ualberta.ca.
authors: Alan
authors: A
authors: Hudson
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D048289:Imidazolidines / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: C531076:1-((imidazolidin-2-yl)imino)indazole; C000601107:7-fluoro-marsanidine; D058647:Adrenergic alpha-2 Receptor Agonists; D006993:Hypnotics and Sedatives; D048289:Imidazolidines; D007191:Indazoles; D009638:Norepinephrine
keywords: Brain microdialysis; Marsanidine; Noradrenaline; α(2)-Adrenoceptors