Pharmacy World and Science

, Volume 17, Issue 6, pp 186–190 | Cite as

Central imidazoline receptors as a target for centrally acting antihypertensive drugs

  • P. A. van Zwieten


Imidazoline (I1)-receptors in the central nervous system play a role in the central regulation of blood pressure and heart rate. Stimulation of these receptors in the rostral ventrolateral medulla induces peripheral sympathoinhibition, and hence a reduction of elevated blood pressure. The imidazoline derivatives moxonidine and rilmenidine are moderately selective I1 receptor stimulants which have been introduced as centrally acting antihypertensives. Since they have little affinity for α2-adrenoceptors, they may be expected to cause less sedation and dry mouth than the α2-adrenoceptor agonists clonidine and methyldopa. The concept of I1 receptors and their agonists therefore offers the possibility to develop centrally acting antihypertensives with a more favourable profile of adverse reactions than the classical α2-adrenoceptor stimulants such as clonidine and methyldopa.


Antihypertensive agents Clonidine Moxonidine Receptors, adrenergic, alpha-2 Receptors, imidazoline Rilmenidine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Van Zwieten PA, Thoolen MJMC, Timmermans PBMWM. The hypotensive activity and side-effects of methyldopa, clonidine and guanfacine. Hypertension 1984;6 Suppl 11: 28–33.Google Scholar
  2. 2.
    Van Zwieten PA, Thoolen MJMC, Timmermans PBMWM. The pharmacological base of the hypotensive activity and side-effects of α-methyl-DOPA, clonidine and guanfacine. Hypertension 1984;6:11–28.Google Scholar
  3. 3.
    Van Zwieten PA. Overview of α2-adrenoceptor agonists with a central action. Am J Cardiol 1986;57:3E-5E.PubMedGoogle Scholar
  4. 4.
    Van Zwieten PA. Different types of centrally acting anti-hypertensive drugs. Eur Heart J 1992;13 Suppl A:18–21.PubMedGoogle Scholar
  5. 5.
    Van Zwieten PA, Chalmers JP. Different types of centrally acting antihypertensives and their targets in the central nervous system. Cardiovasc Drugs Ther 1994;8:787–99.PubMedGoogle Scholar
  6. 6.
    Sen S, Tarazi RC, Bumpus FM. Cardiac hypertrophy and anti-hypertensive therapy. Cardiovasc Res 1977;11:427–33.PubMedGoogle Scholar
  7. 7.
    Henning M. α-methyl-DOPA and related compounds. In: Van Zwieten PA, editor. Handbook of hypertension. Vol. 3. Pharmacology of antihypertensive drugs. Amsterdam: Elsevier, 1984:154–93.Google Scholar
  8. 8.
    Ernsberger P, Giuliano R, Willette RN, Reid DJ. Role of imidazole receptors in the vasodepressor response to clonidine analogs in the rostral ventrolateral medulla. J Pharmacol Exp Ther 1990;253:408–18.PubMedGoogle Scholar
  9. 9.
    Feldman J, Tiberiça E, Bricca G, Dontenwill M, Belcourt A, Bousquet P. Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit. Br J Pharmacol 1990;100:600–4.PubMedGoogle Scholar
  10. 10.
    Haxhiu MA, Dreshaj I, Schäfer SG, Ernsberger P. Selective antihypertensive action of moxonidine is mediated mainly by I1-imidazoline receptors in the rostral ventrolateral medulla. J Cardiovasc Pharmacol 1994;24 Suppl 1:S1–8.Google Scholar
  11. 11.
    Michel MC, Ernsberger P. Keeping an eye on the I site: imidazoline-preferring receptors. Trends Pharmacol Sci 1992;13:369–70.PubMedGoogle Scholar
  12. 12.
    Gomez RE, Ernsberger P, Feinland G, Reis D. Rilmenidine lowers arterial pressure via imidazoline receptors in brain stem C1 area. Eur J Pharmacol 1991;195:181–91.PubMedGoogle Scholar
  13. 13.
    Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ. Agmatine: an endogenous ‘clonidine-displacing’ substance in the brain. Science 1994;263:966–9.PubMedGoogle Scholar
  14. 14.
    Head GA, Saunajust F. Importance of imidazoline receptors in the cardiovascular response to clonidine and rilmenidine in conscious rabbits. Fundam Clin Pharmacol 1992;6 Suppl D:31S-4S.PubMedGoogle Scholar
  15. 15.
    Tibiriça E, Feldman J, Mermet C, Gonon F, Bousquet P. An imidazoline specific mechanism for the hypotensive effect of clonidine: a study with yohimbine and idazoxan. J Pharmacol Exp Ther 1991;256:606–13.PubMedGoogle Scholar
  16. 16.
    Timmermans PBMWM, van Zwieten PA. α-Adrenoceptors: classification, localization, mechanisms, and targets for drugs. J Med Chem 1982;25:1389–401.PubMedGoogle Scholar
  17. 17.
    Ernsberger P, Damon TH, Graff LM, Schäfer SG, Christen MO. Moxonidine, a centrally acting antihypertensive agent, is a selective ligand for I1-imidazoline sites. J Pharmacol Exp Ther 1993;264:172–82.PubMedGoogle Scholar
  18. 18.
    Michel MC, Insel PA. Are there multiple imidazoline binding sites?Trends Pharmacol Sci 1989;10:342–4.PubMedGoogle Scholar
  19. 19.
    Ollivier JP, Christen MO. I1-imidazoline-receptor agonists in the treatment of hypertension: an appraisal of clinical experience. J Cardiovasc Pharmacol 1994;24 Suppl 1:S39–48.Google Scholar
  20. 20.
    Prichard BNC. Clinical experience with moxonidine. Cardiovasc Drugs Ther 1994, 8:49–58.PubMedGoogle Scholar
  21. 21.
    Ernsberger P, Westbrooks KL, Christen MO, Schäfer SG. A second generation of centrally acting antihypertensives acts on putative I1-imidazoline receptors. J Cardiovasc Pharmacol 1992;20 Suppl 4:S1–10.Google Scholar
  22. 22.
    Chrisp P, Faulds D. Moxonidine. Drugs 1992;44:993–1012.Google Scholar
  23. 23.
    Dollery CT. Rilmenidine in mild to moderate hypertension. A double-blind, randomised, parallel group multicenter comparison with methyldopa in 157 patients. Curr Ther Res 1990;47:194–221.Google Scholar
  24. 24.
    Harron DWG. Clinical pharmacology of imidazolines and related compounds. Fundam Clin Pharmacol 1992;6 Suppl 1:41S-4S.PubMedGoogle Scholar
  25. 25.
    Parini A, Bousquet P. From α2-adrenoceptors to imidazoline preferring receptors. Fundam Clin Pharmacol 1992;6 Suppl 1:1S-63S.Google Scholar
  26. 26.
    Motz W, Strauer BE. Therapy of hypertensive cardiac hypertrophy and impaired coronary microcirculation. J Cardiovasc Pharmacol 1994;24 Suppl 1:S34–8.PubMedGoogle Scholar
  27. 27.
    Weitzel G, Pfeiffer B, Stock W. Insulin-like partial effects of agmatine derivatives in adipocytes. Hoppe Seyler's Z Physiol Chem 1980;361:51–60.PubMedGoogle Scholar
  28. 28.
    Kaan EC, Brückner R, Frohly P, Tulp M, Schäfer SG, Zügler D. Effects of agmatine and moxonidine on glucose metabolism. Cardiovasc Risk Factors 1995. In press.Google Scholar

Copyright information

© Royal Dutch Association for the Advancement of Pharmacy 1995

Authors and Affiliations

  • P. A. van Zwieten
    • 1
  1. 1.Departments of Pharmacotherapy and Cardiology, Academic Medical CenterUniversity of AmsterdamAZ Amsterdamthe Netherlands

Personalised recommendations