Six normal subjects were given clonidine infusions after 0, 1 and 3 weeks of treatment with desipramine (2 mg/kgm) and at 1 and 3 weeks after withdrawal from desipramine. The sedative and hypotensive effects of clonidine were inhibited after one and three weeks of desipramine treatment, and returned to normal after stopping treatment without any rebound increase. Such a time-course can be explained in terms of the acute effects of the drug, no adaptive changes at receptors need be invoked.
By contrast, the growth hormone response to clonidine tended to be increased after one week of desipramine, reduced after three weeks of treatment, and further reduced after discontinuation. Such a time-course is consistent with an adaptive down regulation at α2 adrenoceptors in response to their acute stimulation, due to noradrenaline re-uptake blockade.