The brain's own clonidine: purification and characterization of endogenous clonidine displacing substance from brain.

An endogenous clonidine-like substance was isolated from bovine brain and characterized by its chemical and pharmacological properties. The clonidine displacing substance (CDS) is a noncatecholamine, nonpeptide compound. It is devoid of NH2-group, is thermostable, and has a molecular weight of 587.8 +/- 2 daltons. CDS binds selectively to alpha 2-adrenergic receptors in rat brain membranes as measured by displacement of specifically bound [3H]clonidine, an alpha 2-adrenergic agonist, and [3H]rauwolscine, an alpha 2-antagonist, with no affinity for alpha 1-adrenergic receptors. In physiological studies CDS mimics clonidine's action as an inhibitor of the electrically induced twitch response and as a partial agonist of the epinephrine-induced platelet aggregation. At the central nervous system CDS antagonizes clonidine action, increases mean arterial pressure when injected into the nucleus reticularis lateralis of rats, and reduces the hypotensive effect upon intracisternal injection. CDS, which interacts at alpha 2-adrenergic receptors and increases mean arterial pressure upon intracerebral injection, may represent a neuroregulator that plays an important role in cardiovascular events.