Specific binding of threo 1-(1-[2-(1,4-benzodioxane-2-yl)-2-hydroxyethyl]4-piperidyl)-2-benzimidazolinone (R 29814), to rat brain membranes.
The binding of 3[H]R 29814, the pharmacologically less active threoisomer of the potent hypotensive agent erythro-R 28935, was assayed in rat brain membranes and compared with published data on 3[H]R 28935 binding. The 3[H]R 29814 bound to homogenates of rat brain with one saturable component with high affinity (KD = 1.1 nM). The specific binding was rapid and reversible. It was not affected by sodium or magnesium ions, or by guanosine triphosphate. The maximum number of binding sites amounted to approximately 135 fmol/mg protein. The drug specificity of the 3[H]R 29814 binding site was not associated with that of any known drug recognition site, but corresponded to that of erythro 3[H]R 28935. A linear relationship was derived between the affinities of drugs for inhibiting 3[H]R 29814 and 3[H]R 28935 binding. The results suggest that identical sites were labeled by 3[H]R 29814 and 3[H]R 28935 in rat brain membranes with comparable affinity. Since the hypotensive activities of R 29814 and R 28935 greatly differ, it is concluded that the high affinity binding sites of 3[H]R 29814 as well as those of 3[H]R 28935 are not compatible with the sites responsible for the hypotensive effect.
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism*; D001562:Benzimidazoles / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism*; D004147:Dioxins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D004146:Dioxanes; D004147:Dioxins; C010402:R 28935