Comparison of the actions of centrally and peripherally administered clonidine and guanfacine in the rabbit: investigation of the differences.

1 Guanfacine was administered intravenously to rabbits and produced a dose-dependent lowering of blood pressure. 2 Clonidine and guanfacine, administered to rabbits intravenously (30 micrograms/kg and 300 micrograms/kg respectively) and intracisternally (3 micrograms/kg and 12 micrograms/kg respectively) caused a similar degree of hypotension, apparently of central origin. 3 Saliva flow in vivo was estimated. Clonidine (30 micrograms/kg, i.v.) caused a significant decrease in salivation (P less than 0.05) for the first 50 min after injection. Guanfacine caused a significant fall (P less than 0.05) only at 50 and 180 min after injection. 4 Apparent partition coefficients for an octanol/buffer system at pH 7.4 for clonidine and guanfacine were 5.4 and 21.2 respectively. 5 Measurement of guanfacine levels concurrently in both plasma and brain showed that guanfacine had higher brain than plasma levels and that the brain levels were fairly constant over the 3 h measured. Brain:plasma ratios were 2.1:1, 5.3:1 and 13.6:1 after 15, 90 and 180 min respectively. 6 These results suggest that the long duration of action of guanfacine is due to its persistence at its central site of action.