COMPARISON OF THE ACTIONS OF CENTRALLY AND PERIPHERALLY ADMINISTERED CLONIDINE AND GUANFACINE IN THE RABBIT: INVESTIGATION OF THE DIFFERENCES

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Abstract
Guanfacine was administered i.v. to rabbits and produced a dose-dependent lowering of blood pressure. Clonidine and guanfacine [antihypertensive agents], administered to rabbits i.v. (30 and 300 .mu.g/kg, respectively) and intracisternally (3 and 12 .mu.g/kg, respectively) caused a similar degree of hypotension apparently of central origin. Saliva flow in vivo was estimated. Clonidine (30 .mu.g/kg i.v.) caused a significant decrease in salivation (P < 0.05) for the first 50 min after injection. Guanfacine caused a significant fall (P < 0.05) only at 50 and 180 min after injection. Apparent partition coefficients for an octanol/buffer system at pH 7.4 for clonidine and guanfacine were 5.4 and 21.2, respectively. 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. The long duration of action of guanfacine is apparently due to its persistence at its central site of action.