The alpha2 agonist, clonidine, improves spatial working performance in Parkinson's disease.

Previous work has shown that the dopaminergic defect in Parkinson's disease is involved, to some extent, in the "frontal"-like impairment in spatial working memory and attentional set-shifting functions. We investigated whether an alpha2 agonist, clonidine (0.5 and 2 microg/kg, per os), could alleviate spatial working memory and attentional set-shifting defect in Parkinson's disease patients. We observed that 2 microg/kg clonidine stimulated spatial working memory accuracy, but had no effect on attentional set shifting or visual recognition memory. Clonidine was also effective in stimulating spatial working memory after withdrawal of dopaminergic drugs, and when this was done, its effect was greater in severe Parkinson's disease patients. In contrast, clonidine failed to stimulate visual recognition memory. These results suggest that disrupted activation of alpha2 adrenoceptors may contribute to the impairment of spatial working memory in Parkinson's disease.