Clonidine, but not Guanfacine, Impairs Choice Reaction Time Performance in Young Healthy Volunteers

The present study compares the effects of two α2-adrenoceptor agonists, clonidine (0.5, 2, and 5 μg/kg, p.o.), and guanfacine (7 and 29 μg/kg, p.o.), in young healthy volunteers on attentional performance. A placebo-controlled double-blind cross-over design (one drug dose/group) was employed. Neither of the drugs affected measures of motor performance or performance at easy levels in an attentional test. However, at the most difficult level in the attentional test, the highest dose of clonidine (5 μg/kg), but not guanfacine, decreased the number of correct responses and increased reaction latency. Clonidine 5 and guanfacine 29 μg/kg equally increased subjective feelings of sedation and reduced systolic and diastolic blood pressures. Thus, the effects of the drugs on attentional performance could be dissociated from their sedative effects. The results demonstrate that clonidine, but not guanfacine, disrupts performance in an attentional task requiring effortful processing, while leaving performance intact in tests requiring more automatic processing. The lower α2A- vs. α2C-adrenoceptor selectivity ratio of clonidine and the affinity for α1-adrenoceptors of clonidine may be responsible for the different action of these drugs on attention.