Abstract
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.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bream J. B., Lauener H., Picard C. W., Scholtysik G., White T. G. Substituted phenylacetylguanidines: a new class of antihypertensive agents. Arzneimittelforschung. 1975 Oct;25(10):1477–1482. [PubMed] [Google Scholar]
- Chalmers J. P., Reid J. L. Participation of central noradrenergic neurons in arterial baroreceptor reflexes in the rabbit. A study with intracisternally administered 6-hydroxydopamine. Circ Res. 1972 Nov;31(5):789–804. doi: 10.1161/01.res.31.5.789. [DOI] [PubMed] [Google Scholar]
- Cho A. K., Curry S. H. The physiological disposition of 2(2,6-dichloroanilino)-2-imidazoline (St-155). Biochem Pharmacol. 1969 Feb;18(2):511–520. doi: 10.1016/0006-2952(69)90227-5. [DOI] [PubMed] [Google Scholar]
- Dollery C. T., Davies D. S. Centrally acting drugs in antihypertensive therapy. Br J Clin Pharmacol. 1980;10 (Suppl 1):5S–12S. doi: 10.1111/j.1365-2125.1980.tb04898.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dollery C. T., Davies D. S., Draffan G. H., Dargie H. J., Dean C. R., Reid J. L., Clare R. A., Murray S. Clinical pharmacology and pharmacokinetics of clonidine. Clin Pharmacol Ther. 1976 Jan;19(1):11–17. doi: 10.1002/cpt197619111. [DOI] [PubMed] [Google Scholar]
- Dubach U. C., Huwyler R., Radielovic P., Singeisen M. A new centrally action antihypertensive agent guanfacine (BS 100-141). Arzneimittelforschung. 1977;27(3):674–676. [PubMed] [Google Scholar]
- Reid J. L., Barber N. D., Davies D. S. The clinical pharmacology of clonidine: relationship between plasma concentration and pharmacological effect in animals and man. Arch Int Pharmacodyn Ther. 1980;Suppl:11–16. [PubMed] [Google Scholar]
- Reid J. L., Zamboulis C., Hamilton C. A. Guanfacine: effects of long-term treatment and withdrawal. Br J Clin Pharmacol. 1980;10 (Suppl 1):183S–188S. doi: 10.1111/j.1365-2125.1980.tb04928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scholtysik G., Lauener H., Eichenberger E., Bürki H., Salzmann R., Müller-Schweinitzer E., Waite R. Pharmacological actions of the antihypertensive agent N-amidino-2-(2,6-dichlorophenyl)acetamide hydrochloride (BS 100-141). Arzneimittelforschung. 1975 Oct;25(10):1483–1491. [PubMed] [Google Scholar]
- Timmermans P. B., van Zwieten P. A. Mini-review. The postsynaptic alpha 2-adrenoreceptor. J Auton Pharmacol. 1981 Mar;1(2):171–183. doi: 10.1111/j.1474-8673.1981.tb00509.x. [DOI] [PubMed] [Google Scholar]