[3H] UK-14,304, a new agonist ligand of alpha 2-adrenoceptors: a comparative study with human and rat tissue.

[3H] UK-14,304 was used to investigate alpha 2-adrenoceptors in rat brain and human platelets. Receptor pharmacology revealed that the ligand binds with high affinity to alpha 2-adrenoceptors. Psychoactive substances like neuroleptics, antidepressants, and beta-carbolines displace [3H] UK-14,304 from its binding sites in the lower micromolar range. A Hill number around 2 for most neuroleptics suggests a positive cooperativity with the alpha 2-adrenoceptors. Comparative studies with [3H] UK-14,304 and [3H] clonidine utilizing platelet membranes from human volunteers demonstrated that the former ligand is more suitable to investigate possible changes of alpha 2-adrenoceptors; [3H] UK-14,304 labels more receptors with a lower standard deviation, whereby the volume of the blood sample amounted to 35 ml instead of 50 ml required for [3H] clonidine as ligand. No sex differences of binding constants were detected, however an inverse correlation of maximum number of binding sites and affinity was found for female subjects with both ligands. No age-dependent changes of Bmax and KD-values were observed in the range of 24 to 59 years.