Abstract
1. Clonidine (1 μg/kg), given by intracisternal injection to anaesthetized rabbits, lowered mean arterial blood pressure by 33 mmHg and heart rate by 32 beats/min.
2. In animals pre-treated with 6-hydroxydopamine (6-OHD 500 μg/kg intracisternally) 7-10 days before, intracisternal clonidine (1 μg/kg) reduced mean arterial blood pressure by only 2·5 mmHg and heart rate by 4 beats/minute.
3. The hypotensive action of intravenous clonidine was reduced to 49% of control by pre-treatment with intracisternal 6-OHD. In unanaesthetized normal animals intravenous clonidine (30 μg/kg) lowered mean arterial blood pressure by 19·3 mmHg, while after 6-OHD it fell only 9·4 mmHg.
4. These studies suggest that the central hypotensive effect of clonidine is dependent on the integrity of central monoaminergic neurones.
Full text
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ANTON A. H., SAYRE D. F. A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther. 1962 Dec;138:360–375. [PubMed] [Google Scholar]
- Bloom F. E., Algeri S., Groppetti A., Revuelta A., Costa E. Lesions of central norepinephrine terminals with 6-OH-dopamine: biochemistry and fine structure. Science. 1969 Dec 5;166(3910):1284–1286. doi: 10.1126/science.166.3910.1284. [DOI] [PubMed] [Google Scholar]
- Bolme P., Fuxe K. Pharmacological studies on the hypotensive effects of clonidine. Eur J Pharmacol. 1971 Jan;13(2):168–174. doi: 10.1016/0014-2999(71)90147-6. [DOI] [PubMed] [Google Scholar]
- Breese G. R., Traylor T. D. Depletion of brain noradrenaline and dopamine by 6-hydroxydopamine. Br J Pharmacol. 1971 May;42(1):88–99. doi: 10.1111/j.1476-5381.1971.tb07089.x. [DOI] [PMC free article] [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]
- Chalmers J. P., Reid J. L. The effects of intracisternal 6-hydroxydopamine on the development of neurogenic hypertension in the rabbit. J Physiol. 1971 Dec;219(2):20P–21P. [PubMed] [Google Scholar]
- Chalmers J. P., Wurtman R. J. Participation of central noradrenergic neurons in arterial baroreceptor reflexes in the rabbit. Circ Res. 1971 Apr;28(4):480–491. doi: 10.1161/01.res.28.4.480. [DOI] [PubMed] [Google Scholar]
- Chalmers J. P., Wurtman R. J. The fate of intracisternally administered norepinephrine-3H in the brain and spinal cord of the rabbit. J Pharmacol Exp Ther. 1971 Jul;178(1):8–19. [PubMed] [Google Scholar]
- Farnebo L. O., Hamberger B. Drug-induced changes in the release of ( 3 H)-noradrenaline from field stimulated rat iris. Br J Pharmacol. 1971 Sep;43(1):97–106. doi: 10.1111/j.1476-5381.1971.tb07160.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finch L., Haeusler G., Thoenen H. Proceedings: Failure to induce experimental hypertension in rats after intraventricular injection of 6-hydroxydopamine. Br J Pharmacol. 1972 Feb;44(2):356P–357P. [PMC free article] [PubMed] [Google Scholar]
- GOERANSSON G. THE METABOLISM OF FATTY ACIDS IN THE RAT. VI. ARACHIDONIC ACID. Acta Physiol Scand. 1965 May-Jun;64:1–5. doi: 10.1111/j.1748-1716.1965.tb04148.x. [DOI] [PubMed] [Google Scholar]
- Haeusler G. Early pre- and postjunctional effects of 6-hydroxydopamine. J Pharmacol Exp Ther. 1971 Jul;178(1):49–62. [PubMed] [Google Scholar]
- Hoefke W., Kobinger W. Pharmakologische Wirkungen des 2-(2,6-Dichlorphenylamino)-2-imidazolin-hydrochlorids, einer neuen, antihypertensiven Substanz. Arzneimittelforschung. 1966 Aug;16(8):1038–1050. [PubMed] [Google Scholar]
- Iversen L. L., Uretsky N. J. Regional effects of 6-hydroxydopamine on catecholamine containing neurones in rat brain and spinal cord. Brain Res. 1970 Dec 1;24(2):364–367. doi: 10.1016/0006-8993(70)90121-6. [DOI] [PubMed] [Google Scholar]
- Kaplan H. R., La Sala S. A., Simon A., Robson R. D. ST 155-induced cardiac slowing in dogs. Eur J Pharmacol. 1969 May;6(2):193–196. doi: 10.1016/0014-2999(69)90218-0. [DOI] [PubMed] [Google Scholar]
- Klupp H., Knappen F., Otsuka Y., Streller I., Teichmann H. Effects of Clonidine on central sympathetic tone. Eur J Pharmacol. 1970 May;10(2):225–229. doi: 10.1016/0014-2999(70)90276-1. [DOI] [PubMed] [Google Scholar]
- Kobinger W., Oda M. Effects of sympathetic blocking substances on the diving reflex of ducks. Eur J Pharmacol. 1969 Sep;7(3):289–295. doi: 10.1016/0014-2999(69)90094-6. [DOI] [PubMed] [Google Scholar]
- Kobinger W., Walland A. Investigations into the mechanism of the hypotensive effect of 2-(2,6-dichlorphenylamino)-2-imidazoline-HCl. Eur J Pharmacol. 1967 Dec;2(3):155–162. doi: 10.1016/0014-2999(67)90080-5. [DOI] [PubMed] [Google Scholar]
- Kobinger W., Walland A. Involvement of adrenergic receptors in central vagus activity. Eur J Pharmacol. 1971 Sep;16(1):120–122. doi: 10.1016/0014-2999(71)90066-5. [DOI] [PubMed] [Google Scholar]
- Kobinger W., Walland A. Kreislaufuntersuchungen mit 2-(2,6-Dichlorphenylamino)-2-imidazolin-hydrochlorid. Arzneimittelforschung. 1967 Mar;17(3):292–300. [PubMed] [Google Scholar]
- Korner P. I., Uther J. B., White S. W. Circulatory effects of chloralose-urethane and sodium pentobarbitone anaesthesis in the rabbit. J Physiol. 1968 Dec;199(2):253–265. doi: 10.1113/jphysiol.1968.sp008652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LAVERTY R., SHARMAN D. F., VOGT M. ACTION OF 2, 4, 5-TRIHYDROXYPHENYLETHYLAMINE ON THE STORAGE AND RELEASE OF NORADRENALINE. Br J Pharmacol Chemother. 1965 Apr;24:549–560. doi: 10.1111/j.1476-5381.1965.tb01745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MCCUBBIN J. W., KANEKO Y., PAGE I. H. Ability of serotonin and norepinephrine to mimic the central effects of reserpine on vasomotor activity. Circ Res. 1960 Jul;8:849–858. doi: 10.1161/01.res.8.4.849. [DOI] [PubMed] [Google Scholar]
- Muir A. L., Burton J. L., Lawrie D. M. Circulatory effects at rest and exercise of clonidine, an imidazoline derivative with hypotensive properties. Lancet. 1969 Jul 26;2(7613):181–184. doi: 10.1016/s0140-6736(69)91423-8. [DOI] [PubMed] [Google Scholar]
- PORTER C. C., TOTARO J. A., STONE C. A. Effect of 6-hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice. J Pharmacol Exp Ther. 1963 Jun;140:308–316. [PubMed] [Google Scholar]
- Parsons W. B., Jr, Morledge J. H. Antihypertensive effect of a new imidazoline compound (clonidine) and chlorthalidone, individually and in combination. Am J Cardiol. 1970 Sep;26(3):258–261. doi: 10.1016/0002-9149(70)90792-7. [DOI] [PubMed] [Google Scholar]
- Robson R. D., Kaplan H. R. An involvement of St 155 [2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride, catapres] in cholinergic mechanisms. Eur J Pharmacol. 1969 Mar;5(4):328–337. doi: 10.1016/0014-2999(69)90109-5. [DOI] [PubMed] [Google Scholar]
- SHARE N. N., MELVILLE K. I. Centrally mediated sympathetic cardiovascular responses induced by intraventricular norepinephrine. J Pharmacol Exp Ther. 1963 Jul;141:15–21. [PubMed] [Google Scholar]
- Sattler R. W., van Zwieten P. A. Acute hypotensive action of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155) after infusion into the cat's vertebral artery. Eur J Pharmacol. 1967 Oct;2(1):9–13. doi: 10.1016/0014-2999(67)90016-7. [DOI] [PubMed] [Google Scholar]
- Schmitt H., Boissier J. R., Giudicelli J. F., Fichelle J. Cardiovascular effects of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (ST 155). II. Central sympathetic structures. Eur J Pharmacol. 1968 Mar;2(5):340–346. doi: 10.1016/0014-2999(68)90184-2. [DOI] [PubMed] [Google Scholar]
- Schmitt H., Schmitt H. Localization of the hypotenisve effect of 2-(2-6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155, Catapresan). Eur J Pharmacol. 1969 Apr;6(1):8–12. doi: 10.1016/0014-2999(69)90057-0. [DOI] [PubMed] [Google Scholar]
- Shaw J., Hunyer S. N., Korner P. I. Sites of central nervous action of clonidine on reflex autonomic function in the unanaesthetized rabbit. Eur J Pharmacol. 1971 Jun;15(1):66–78. doi: 10.1016/0014-2999(71)90080-x. [DOI] [PubMed] [Google Scholar]
- Shaw J., Hunyor S. N., Korner P. I. The peripheral circulatory effects of clonidine and their role in the production of arterial hypotension. Eur J Pharmacol. 1971 Apr;14(2):101–111. doi: 10.1016/0014-2999(71)90203-2. [DOI] [PubMed] [Google Scholar]
- Sherman G. P., Grega G. J., Woods R. J., Buckley J. P. Evidence for a central hypotensive mechanism of 2-(2,6-dichlorophenylamino)-2-imidazoline (Catapresan, ST-155). Eur J Pharmacol. 1968 Feb;2(4):326–328. doi: 10.1016/0014-2999(68)90087-3. [DOI] [PubMed] [Google Scholar]
- Starke K., Wagner J., Schümann H. J. Adrenergic neuron blockade by clonidine: comparison with guanethidine and local anesthetics. Arch Int Pharmacodyn Ther. 1972 Feb;195(2):291–308. [PubMed] [Google Scholar]
- Thoenen H., Tranzer J. P. Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-Hydroxydopamine. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1968;261(3):271–288. doi: 10.1007/BF00536990. [DOI] [PubMed] [Google Scholar]
- Toda N., Matsuda Y., Shimamoto K. Cardiovascular effects of sympathomimetic amines injected into the cerebral ventricles of rabbits. Int J Neuropharmacol. 1969 Sep;8(5):451–461. doi: 10.1016/0028-3908(69)90061-6. [DOI] [PubMed] [Google Scholar]
- Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol. 1968 Dec;5(1):107–110. doi: 10.1016/0014-2999(68)90164-7. [DOI] [PubMed] [Google Scholar]
- Uretsky N. J., Iversen L. L. Effects of 6-hydroxydopamine on catecholamine containing neurones in the rat brain. J Neurochem. 1970 Feb;17(2):269–278. doi: 10.1111/j.1471-4159.1970.tb02210.x. [DOI] [PubMed] [Google Scholar]
- Zaimis E., Hanington E. A possible pharmacological approach to migraine. Lancet. 1969 Aug 9;2(7615):298–300. doi: 10.1016/s0140-6736(69)90058-0. [DOI] [PubMed] [Google Scholar]
- von EULER U., LISHAJKO F. Improved technique for the fluorimetric estimation of catecholamines. Acta Physiol Scand. 1961 Apr;51:348–355. doi: 10.1111/j.1748-1716.1961.tb02128.x. [DOI] [PubMed] [Google Scholar]