The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors.

We have determined the binding affinities of the novel alpha-2 adrenoceptor antagonist radioligand [3H]-MK912 for the cloned human alpha-2A, alpha-2B and alpha-2C adrenoceptors. The KD-values were 1.25 nM, 1.36 nM and 0.086 nM for the alpha-2A, alpha-2B and alpha-2C subtypes, respectively. Thus, the selectivity of [3H]-MK912 for the human alpha-2C adrenoceptor vs. the human alpha-2A and alpha-2B adrenoceptors is 14-fold and 16-fold, respectively. The alpha-2C selectivity, and the very high affinity of [3H]-MK912 for the alpha-2C adrenoceptor subtype (KD = 86 pM) makes this radioligand a promising tool for studying the role of alpha-2C adrenoceptors in the human. A selection of antagonists useful for differentiating between the human alpha-2A, alpha-2B and alpha-2C adrenoceptor subtypes is discussed.