Site and mode of action of clonidine in the central nervous system.

In urethane-anaesthetized rats clonidine was administered intravenously (i.v.), intracerebroventricularly (i.c.v.) or onto the surface of the area postrema which protrudes into the fourth cerebral ventricle. In each instance clonidine induced a dose-dependent lowering of the blood pressure. The region of the area postrema appears to be the most sensitive site for the action of clonidine so far studied. In order to obtain similar blood pressure effects, approximately 8 times higher amounts were needed i.c.v., and about 80 times higher amounts i.v., than onto the surface of the area postrema. A pretreatment of the rats with the specific histamine H2-receptor blocking drug, metiamide (4.5 micronmoles/rat i.c.v.) shifted the dose-response curve of clonidine (i.c.v.) to the right. The results suggest that clonidine exerts its hypotensive effect in the rat via a stimulation of histamine H2-receptors in, or in the vicinity of, the area postrema.