Skip to main content
SpringerLink
Log in

Evidence for a central postsynaptic action of clonidine

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Intravenous administration of clonidine (1–100 μg/kg) produces a dose-dependent mydriasis in cats by inhibition of parasympathetic tone to the iris. The magnitude of CNS-induced pupillary dilation was similar in both normal anaesthetized cats and in araesthetized preparations pretreated with reserpine (5 mg/kg i.p.) and α-methyl-p-tyrosine (2×300 mg/kg i.p.). Pretreatment reduced the concentrations of noradrenaline, dopamine and serotonin to less than 3% of that control levels in most parts of the CNS in which these amines were measured. Clonidine produced bradycardia in control animals but not in pretreated cats. In amine depleted animals in which only one eye was innervated by the ciliary nerves (parasympathetic), clonidine produced mydriasis only on the innervated side.

These experiments confirm our previous observations that clonidine produces mydriasis in the cat by means of inhibition of parasympathetic tone to the iris. It is concluded that if clonidine produces this effect by stimulating noradrenergic, dopaminergic or serotonergic receptors, then clonidine exerts its centrally-induced mydriatic effect by acting on post-synaptic mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andén, N. E., Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T.: Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci. 9, 513–523 (1970)

    Google Scholar 

  • Boissier, J. R., Giudicelli, J. F., Fichelle, J., Schmitt, H., Schmitt, H.: Cardiovascular effects of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (ST 155). I. Peripheral sympathetic system. Eur. J. Pharmacol. 2, 333–339 (1968)

    Google Scholar 

  • Bolme, P., Corrodi, H., Fuxe, K., Hökfelt, T. Lidbrink, P., Goldstein, M.: Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. Eur. J. Pharmacol. 28, 89–94 (1974)

    Google Scholar 

  • Briant, R. H., Reid, J. L., Dollery, C. T.: Interaction between clonidine and desipramine in man. Br. Med. J. 1, 522–523 (1973)

    Google Scholar 

  • Dollery, C. T., Reid, J. L.: Central noradrenergic neurones and the cardiovascular actions of clonidine in the rabbit. Br. J. Pharmacol. 47, 206–216 (1973)

    Google Scholar 

  • Enero, M. A., Langer, S. Z., Rothlin, R. P., Stefano, F. J. E.: Role of the α-adrenoceptor in regulating noradrenaline overflow by nerve stimulation. Br. J. Pharmacol. 44, 672–688 (1972)

    Google Scholar 

  • Farnebo, L.-O., Hamberger, B.: Drug-induced changes in the release of [3H]-noradrenaline from field stimulated rat iris. Br. J. Pharmacol. 43, 97–106 (1971a)

    Google Scholar 

  • Farnebo, L.-O., Hamberger, B.: Drug-induced changes in the release of 3H-monoamines from field stimulated rat brain slices. Acta Physiol. Scand., Suppl. 371, 35–44 (1971b)

    Google Scholar 

  • Franz, D. N., Hare, B. D., Neumayr, R. J.: Depression of sympathetic preganglionic neurons by clonidine: evidence for stimulation of 5-HT receptors. Clin. Exp. Hyperten. 1, 115–140 (1978)

    Google Scholar 

  • Haeusler, G.: Activation of the central pathway of the baroreceptor reflex, a possible mechanism of the hypotensive action of clonidine. Naunyn-Schmiedeberg's Arch. Pharmacol 278, 231–246 (1973)

    Google Scholar 

  • Haeusler, G.: Clonidine-induced inhibition of sympathetic nerve activity: No indication for a central presynaptic or an indirect sympathomimetic mode of action. Naunyn-Schmiedeberg's Arch. Pharmacol. 286, 97–111 (1974)

    Google Scholar 

  • Hoefke, W., Warnke-Sachs, E.: Influence of desmethylimipramine on the hypotensive effect of clonidine. Arzneim.-Forsch. (Drug Res.) 24, 1046–1047 (1974)

    Google Scholar 

  • Hoyer, I., van Zwieten, P. A.: The central hypotensive action of amphetamine, ephedrine, phentermine, chlorphentermine and fenfluramine. J. Pharm. Pharmacol. 24, 452–458 (1972)

    Google Scholar 

  • Kissinger, P. T.: Amperometric and coulometric detectors for highperformance liquid chromatography. Anal. Chem. 49, 447–456A (1977)

    Google Scholar 

  • Klupp, H., Knappen, F., Otsuka, Y., Streller, I., Teichmann, H.: Effects of clonidine on central sympathetic tone. Eur. J. Pharmacol. 10, 225–229 (1970)

    Google Scholar 

  • Kobinger, W.: Central α-adrenergic systems as targets for hypotensive drugs. Rev Physiol. Biochem. Pharmacol. 81, 39–100 (1978)

    Google Scholar 

  • Kobinger, W., Pichler, L.: The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline. Eur. J. Pharmacol. 30, 56–62 (1975)

    Google Scholar 

  • Kobinger, W. Walland, A.: Investigations into the mechanism of the hypotensive effect of 2-(2,6-dichlorophenylamino)-2-imidazoline-HCl. Eur. J. Pharmacol 2, 155–162 (1967)

    Google Scholar 

  • Kobinger, W., Walland, A.: Facilitation of vagal reflex bradycardia by an action of clonidine on central α-receptors. Eur. J. Pharmacol. 19, 210–217 (1972)

    Google Scholar 

  • Koss, M. C.: Effect of clonidine and chlorpromazine on centrally evoked electrodermal responses and their interaction with yohimbine. Eur. J. Pharmacol. 41, 221–224 (1977)

    Google Scholar 

  • Koss, M. C., Davison, M. A.: The electrodermal response as a model for central sympathetic reactivity: the action of clonidine. Eur. J. Pharmacol. 37, 71–78 (1976)

    Google Scholar 

  • Koss, M. C., Rieger, J. A.: Differential transmission in the superior cervical ganglion of the cat. J. Pharmacol. Exp. Ther. 199, 538–543 (1976)

    Google Scholar 

  • Koss, M. C., San, L. C.: Analysis of clonidine-induced mydriasis. Invest. Ophthal. 15, 566–570 (1976)

    Google Scholar 

  • Langer, S. Z.: The regulation of transmitter release elicited by nerve stimulation through a presynaptic feed-back mechanism. (E. Usdin and S. H. Snyder (eds.), In: Frontiers in catecholamine research, pp. 543–549. Oxford: Pergamon Press 1973

    Google Scholar 

  • Rand, M. J., Rush, M., Wilson, J.: Some observations on the inhibition of salivation of ST 155 [2-(2,6-dichlorophenylamine)-2-imidazoline hydrochloride, Catapres, Catapresan]. Eur. J. Pharmacol. 5, 168–172 (1969)

    Google Scholar 

  • Reid, J. L., Briant, R. H., Dollery, C. T.: Desmethylimipramine and the hypotensive action of clonidine in the rabbit. Life Sci. 12, 459–467 (1973)

    Google Scholar 

  • Sasa, S., Blank, L. C.: Simultaneous determination of norepinephrine, dopamine, and serotonin in brain tissues. Anal. Chim. Acta (in press, 1979)

  • 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. 2, 9–13 (1967)

    Google Scholar 

  • Schmitt, H., 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. 2, 340–346 (1968)

    Google Scholar 

  • Schmitt, H., Schmitt, H., Fénard, S.: Evidence for an α-sympathomimetic component in the effects of catapresan on vasomotor centres: antagonism by piperoxane. Eur. J. Pharmacol. 14, 98–100 (1971)

    Google Scholar 

  • Schmitt, H., Schmitt, H., Fénard, S.: Action of α-adrenergic blocking drugs on the sympathetic centres and their interactions with the central sympatho-inhibitory effect of clonidine. Arzneim-Forsch. (Drug. Res.) 23, 40–45 (1973)

    Google Scholar 

  • Sharpe, L. G., Pickworth, W. B., Martin, W. R.: Actions of amphetamine and antagonists on pupil diameter in the chronic sympathectomized dog. Psychopharmacology 53, 115–120 (1977)

    Google Scholar 

  • Shore, P. A., Olin, J. S.: Identification and chemical assay of norepinephrine in brain and other tissues. J. Pharmacol. Exp. Ther. 122, 295–300 (1958)

    Google Scholar 

  • Starke, K., Altmann, K. P.: Inhibition of adrenergic neurotransmission by clonidine: an action on prejunctional α-recptors. Neuropharmacology 12, 339–347 (1973)

    Google Scholar 

  • Starke, K., Borowski, E., Endo, T.: Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur. J. Pharmacol. 34, 385–388 (1975)

    Google Scholar 

  • Starke, K., Montel, H.: Involvement of α-receptors in clonidineinduced inhibition of transmitter release from central monoamine neurones. Neuropharmacology 12, 1073–1080 (1973)

    Google Scholar 

  • Ury, B., Gellhorn, E.: Role of the sympathetic system in reflex dilatation of pupil. J. Neurophysiol. 2, 268–275 (1939)

    Google Scholar 

  • van Rossum, J. M.: Different types of sympathomimetic α-receptors. J. Pharm. Pharmacol. 17, 202–216 (1965)

    Google Scholar 

  • van Spanning, H. W., van Zwieten, P. A.: The interference of tricyclic antidepressants with the central hypotensive effect of clonidine. Eur. J. Pharmacol. 24, 402–404 (1973)

    Google Scholar 

  • Warnke, E., Hoefke, W.: Influence of central pretreatment with 6-hydroxydopamine on the hypotensive effect of clonidine. Arzneim.-Forsch. (Drug Res.) 27, 2311–2313 (1977)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Oklahoma Health Sciences Center, P.O. Box 26901, 73190, Oklahoma City, Oklahoma, USA

    M. C. Koss & H. D. Christensen

  2. Department of Ophthalmology, University of Oklahoma Health Sciences Center, P.O. Box 26901, 73190, Oklahoma City, Oklahoma, USA

    M. C. Koss & H. D. Christensen

  3. Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, P.O. Box 26901, 73190, Oklahoma City, Oklahoma, USA

    M. C. Koss & H. D. Christensen

Authors
  1. M. C. Koss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. D. Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koss, M.C., Christensen, H.D. Evidence for a central postsynaptic action of clonidine. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 45–50 (1979). https://doi.org/10.1007/BF00506550

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00506550

Key words

Search

Navigation