Use of a sympathetic-cholinergic system in the analysis of sympatho-inhibition produced by clonidine and some congeneric derivatives of clonidine.

The effects of clonidine and five analogs of clonidine were tested with regard to their ability to depress centrally and peripherally evoked electrodermal responses (EDR) in control cats, as well as in animals pretreated with yohimbine hydrochloride. With the exception of St-91, all of the clonidine-like substances selectively reduced the amplitude of centrally (hypothalamic) evoked responses in a dose-dependent fashion. Clonidine was found to have no significant inhibitory effect at the level of the sympathetic ganglion. The order of central nervous system sympatho-inhibitory potency of these compounds was clonidine (St-155) greater than St-375 greater than St-606 greater than St-600 greater than St-608 much much greater than St-91. Prior treatment with yohimbine hydrochloride (0.5 mg/kg i.v.) antagonized the depressant effect of all of these drugs. These results indicate that clonidine and the clonidine congeners tested (with the exception of St-91) all produce sympatho-inhibition by an action on a CNS alpha-adrenergic mechanism and demonstrate the usefulness of this electrodermal model system for the analysis of drugs affecting central sympathetic reactivity.