Binding of (+/-)-3H-lofexidine to alpha-adrenoceptors in membranes from rat brain.


The binding of (+/-)-3H-lofexidine (spec. act. 26.8 Ci/mmol) to rat brain membranes was studied. The specific binding of (+/-)-3H-lofexidine, defined as the excess over blanks containing excess (-)-noradrenaline was a saturable process. Scatchard analysis indicated a single class of binding sites (KD = 5.5 nM). The maximal number of binding sites amounted to 280 fmol/mg protein, comparable to the number occupied by 3H-clonidine and 3H-guanfacine. Specific binding reached equilibrium by about 5 min and dissociated in a biphasic manner. A rapid and a slow component of dissociation was found. The specific binding sites identified by (+/-)-3H-lofexidine in rat brain tissue are to be classified as alpha 2-adrenoceptors. Selective agonists as well as antagonists of alpha 1-adrenoceptors were weak displacers of the binding, whereas preferential stimulants as well as blocking drugs of alpha 2-adrenoceptors displayed high affinity for the (+/-)-3H-lofexidine sites. The relative affinity of various drugs for the sites labeled by (+/-)-3H-lofexidine perfectly corresponded with that for the specific binding sites identified by 3H-clonidine and 3H-guanfacine. This study shows the usefulness of (+/-)-3H-lofexidine as an additional radioligand for a direct characterization of alpha 2-adrenoceptors in brain tissue. It is concluded that (+/-)-3H-lofexidine labels the same population of alpha 2-adrenoceptors in rat brain as accessible to 3H-clonidine and 3H-guanfacine.

Cite this paper

@article{Timmermans1983BindingO, title={Binding of (+/-)-3H-lofexidine to alpha-adrenoceptors in membranes from rat brain.}, author={Pieter B. M. WW. M. Timmermans and J E van Kemenade and Y M Harms and G. Prop and Ethan Graf and Pieter A van Zwieten}, journal={Archives internationales de pharmacodynamie et de thérapie}, year={1983}, volume={261 1}, pages={23-35} }