A series of novel imidazoline I2-receptor selective Schiff bases of 1-(benzylidenamino)-3,3-dimethylguanidine.
A series of 12 Schiff bases of 1-(benyzylidenamino)-3,3-dimethylguanidine were evaluated for their affinities at imidazoline I2-receptors and alpha 2-adrenoceptors in the guinea pig cerebral cortex by using a 2-curve assay with [3H]idazoxan as ligand and the simultaneous computer analysis of (-)adrenaline masked and non-masked competition curves. All of the dimethylguanidines were selective for I2-receptors with the selectivity ranging 6-110-fold, and the most selective being WAP8 (2-bromobenzylidenamino-3,3-dimethylguanidine) closely followed by FLA151 (2-chlorobenzylidenamino-3, 3-dimethylguanidine). Some of the dimethylguanidines were also tested for affinity at bovine kidney cortex I2-receptors and guinea pig alpha 1-adrenoceptors. These substances were found to have similar affinities for bovine kidney I2-receptors as for guinea pig cerebral cortex I2-receptors, but their affinities for the alpha 1-adrenoceptors were considerably lower.
Wikberg
J E
JE
Department of Pharmaceutical Biosciences, Uppsala University, Sweden. JWIKBERG@BMC.UU.SE
Hudson
A L
AL
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000648:ultrastructure; D004837:Epinephrine / Q000378:metabolism; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism*; D006168:Guinea Pigs; D019329:Idazoxan / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D054755:Imidazoline Receptors; D007672:Kidney Cortex / Q000648:ultrastructure; D009638:Norepinephrine / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism*; D012545:Schiff Bases / Q000737:chemistry* / Q000378:metabolism*; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism
C105204:2-bromobenzylideneamino-3,3-dimethylguanidine; D006146:Guanidines; D007093:Imidazoles; D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D012545:Schiff Bases; D014316:Tritium; D015016:Yohimbine; C105203:2-chlorobenzylideneamino-3,3-dimethylguanidine; D009638:Norepinephrine; D019329:Idazoxan; D004837:Epinephrine