Abstract
1 The central α-adrenoceptors responsible for mediating clonidine-induced sedation in rats have been characterized according to their sensitivity to α-adrenoceptor agonists and antagonists.
2 Clonidine, injected intraperitoneally or intracerebroventricularly, caused dose-dependent sedation, both in terms of a reduction in the time that rats could remain on an accelerating rotarod and in terms of overt sedation assessed visually. Following intracerebroventricular injection, xylazine, naphazoline and methoxamine, but not phenylephrine, produced similar effects.
3 The sedation caused by intraperitoneal injection of clonidine was antagonized by intracerebroventricularly injected phentolamine, yohimbine, piperoxan and tolazoline but not by labetalol, thymoxamine or prazosin.
4 The relative potencies of the agonists in causing sedation and of the antagonists in inhibiting the sedative effect of clonidine clearly demonstrated that the central α-adrenoceptors mediating clonidine-induced sedation are the same as the peripheral presynaptic α2-adrenoceptors.
5 All the α-adrenoceptor agonists caused hypothermia after intracerebroventricular injection, but their order of potency was different from that in producing sedation. The hypothermic effect of intraperitoneally injected clonidine was little affected by any of the antagonists administered intracerebroventricularly. No conclusions could be drawn concerning the type of receptor responsible for mediating hypothermia.
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Selected References
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- Borowski E., Starke K., Ehrl H., Endo T. A comparison of pre- and postsynaptic effects of alpha-adrenolytic drugs in the pulmonary artery of the rabbit. Neuroscience. 1977;2(2):285–296. doi: 10.1016/0306-4522(77)90095-1. [DOI] [PubMed] [Google Scholar]
- Cavero I., Roach A. G. The effects of prazosin on the clonidine induced hypotension and bradycardia in rats and sedation in chicks [proceedings]. Br J Pharmacol. 1978 Mar;62(3):468P–469P. [PMC free article] [PubMed] [Google Scholar]
- Cedarbaum J. M., Aghajanian G. K. Catecholamine receptors on locus coeruleus neurons: pharmacological characterization. Eur J Pharmacol. 1977 Aug 15;44(4):375–385. doi: 10.1016/0014-2999(77)90312-0. [DOI] [PubMed] [Google Scholar]
- Delbarre B., Schmitt H. A further attempt to characterize sedative receptors activated by clonidine in chickens and mice. Eur J Pharmacol. 1973 Jun;22(3):355–359. doi: 10.1016/0014-2999(73)90038-1. [DOI] [PubMed] [Google Scholar]
- Delbarre B., Schmitt H. Sedative effects of alpha-sympathomimetic drugs and their antagonism by adrenergic and cholinergic blocking drugs. Eur J Pharmacol. 1971;13(3):356–363. doi: 10.1016/0014-2999(71)90226-3. [DOI] [PubMed] [Google Scholar]
- Doxey J. C., Smith C. F., Walker J. M. Selectivity of blocking agents for pre-and postsynaptic alpha-adrenoceptors. Br J Pharmacol. 1977 May;60(1):91–96. doi: 10.1111/j.1476-5381.1977.tb16752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drew G. M. Effects of alpha-adrenoceptor agonists and antagonists on pre- and postsynaptically located alpha-adrenoceptors. Eur J Pharmacol. 1976 Apr;36(2):313–320. doi: 10.1016/0014-2999(76)90084-4. [DOI] [PubMed] [Google Scholar]
- Drew G. M. Pharmacological characterisation of the presynaptic alpha-adrenoceptor in the rat vas deferens. Eur J Pharmacol. 1977 Mar 21;42(2):123–130. doi: 10.1016/0014-2999(77)90351-x. [DOI] [PubMed] [Google Scholar]
- Drew G. M. Pharmacological characterization of the presynaptic alpha-adrenoceptors regulating cholinergic activity in the guinea-pig ileum. Br J Pharmacol. 1978 Oct;64(2):293–300. doi: 10.1111/j.1476-5381.1978.tb17303.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holman R. B., Shillito E. E., Vogt M. Sleep produced by clonidine (2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride). Br J Pharmacol. 1971 Dec;43(4):685–695. doi: 10.1111/j.1476-5381.1971.tb07203.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones B. J., Roberts D. J. The quantiative measurement of motor inco-ordination in naive mice using an acelerating rotarod. J Pharm Pharmacol. 1968 Apr;20(4):302–304. doi: 10.1111/j.2042-7158.1968.tb09743.x. [DOI] [PubMed] [Google Scholar]
- Kleinlogel H., Scholtysik G., Sayers A. C. Effects of clonidine and BS 100-141 on the EEG sleep pattern in rats. Eur J Pharmacol. 1975 Aug;33(1):159–163. doi: 10.1016/0014-2999(75)90151-x. [DOI] [PubMed] [Google Scholar]
- Langer S. Z. Presynaptic regulation of catecholamine release. Biochem Pharmacol. 1974 Jul 1;23(13):1793–1800. doi: 10.1016/0006-2952(74)90187-7. [DOI] [PubMed] [Google Scholar]
- Langer S. Z. Sixth gaddum memorial lecture, National Institute for Medical Research, Mill Hill, January 1977. Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol. 1977 Aug;60(4):481–497. doi: 10.1111/j.1476-5381.1977.tb07526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laverty R. A comparison of the behavioural effects of some hypotensive imidazoline derivatives in rats. Eur J Pharmacol. 1970 Feb;9(2):163–169. doi: 10.1016/0014-2999(70)90295-5. [DOI] [PubMed] [Google Scholar]
- Laverty R., Taylor K. M. Behavioural and biochemical effects of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (St 155) on the central nervous system. Br J Pharmacol. 1969 Feb;35(2):253–264. doi: 10.1111/j.1476-5381.1969.tb07984.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Popick F. R. Application of a new intraventricular injection technique in rat brain norepinephrine studies. Life Sci. 1976 Jan 15;18(2):197–203. doi: 10.1016/0024-3205(76)90025-4. [DOI] [PubMed] [Google Scholar]
- Saameli K., Scholtysik G., Waite R. Pharmacology of BS 100-141, a centrally acting antihypertensive drug. Clin Exp Pharmacol Physiol. 1975;Suppl 2:207–212. [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]
- Starke K. Alpha sympathomimetic inhibition of adrenergic and cholinergic transmission in the rabbit heart. Naunyn Schmiedebergs Arch Pharmacol. 1972;274(1):18–45. doi: 10.1007/BF00501004. [DOI] [PubMed] [Google Scholar]
- Starke K., Borowski E., Endo T. Preferential blockade of presynaptic alpha-adrenoceptors by yohimbine. Eur J Pharmacol. 1975 Dec;34(2):385–388. doi: 10.1016/0014-2999(75)90268-x. [DOI] [PubMed] [Google Scholar]
- Starke K., Endo T., Taube H. D. Relative pre- and postsynaptic potencies of alpha-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn Schmiedebergs Arch Pharmacol. 1975;291(1):55–78. doi: 10.1007/BF00510821. [DOI] [PubMed] [Google Scholar]
- Tsoucaris-Kupfer D., Schmitt H. Hypothermic effect of alpha-sympathomimetic agents and their antagonism by adrenergic and cholinergic blocking drugs. Neuropharmacology. 1972 Sep;11(5):625–635. doi: 10.1016/0028-3908(72)90071-8. [DOI] [PubMed] [Google Scholar]
- Wikberg J. Differentiation between pre- and postjunctional alpha-receptors in guinea pig ileum and rabbit aorta. Acta Physiol Scand. 1978 Jul;103(3):225–239. doi: 10.1111/j.1748-1716.1978.tb06210.x. [DOI] [PubMed] [Google Scholar]
- Zebrowska-Lupina I., Przegalinski E., Sloniec M., Kleinrok Z. Clonidine-induced locomotor hyperactivity in rats. The role of central postsynaptic alpha-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1977 Apr;297(3):227–231. doi: 10.1007/BF00509265. [DOI] [PubMed] [Google Scholar]
