An Affinity Label for α₂‐Adrenergic Receptors in Rat Brain

Clonidine, a potent and highly selective α₂‐adrenergic agonist of the central nervous system, was modified. Insertion of the strong alkylating isothiocyanate group (NCS) group, at its aromatic residue, makes clonidine a potential affinity label of the α₂‐adrenergic receptors. In displacement of [³H]clonidine and p‐[³H]aminoclonidine from rat brain membrane preparations, clonidine‐NCS demonstrates high affinity for the α₂‐adrenergic receptors (K_d= 50 mM). The covalent labelling of the central α₂‐receptors requires higher concentrations of the irreversible ligand (1–70 μM), thus indicating possible non‐productive interactions at the environment of the receptor site. Only partial protection of the receptors is observed with a reversible α₂‐agonist. The new clonidine analog appears to be a general ligand for the α₂‐adrenergic receptors and might serve as a potential affinity probe for these receptors.