Skip to main content
SpringerLink
Log in

Co-dergocrine mesylate inhibits the increase in plasma catecholamines caused by nifedipine in essential hypertension

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Co-dergocrine mesylate (Cod), which inhibits norepinephrine secretion by stimulating presynaptic dopamine receptors, and has no known metabolic side effect, has an additive antihypertensive effect to that of Nifedipine (Nif). Plasma norepinephrine, epinephrine, renin activity and aldosterone have been measured after acute administration of Nif and Cod alone and in combination to 18 patients with a diastolic blood pressure > 105 mm Hg in a cross-over, randomized, double-blind study. Every patient received 4 mg Cod then 20 mg Nif, placebo then 20 mg Nif and 4 mg Cod then placebo. The second treatment was always given 1 h after the first medication. Blood pressure was measured before and every 15 min during the study period. Blood for measurement of catecholamines, aldosterone and renin activity was collected before medication, 1 h after the first dose and 90 min after the second treatment.

Blood pressure was significantly lower (P < 0.05) where Cod preceded Nif. Cod caused a significant decrease in plasma norepinephrine from 293 to 202 pg · ml−1 and in epinephrine from 67 to 55 pg · ml−1. The Nif-induced increase in norepinephrine from a pre-treatment value of 293 pg · ml−1 with preceding Cod to 331 pg · ml−1 was much less than the increase with placebo as premedication, from 284 to 440 pg · ml−1. Nif caused an increase in renin activity but no increase in aldosterone.

Nif-related side effects, such as flushing and headache, occurred in 6 patients of whom 5 had no received Cod as premedication. Due to the stabilizing action of Cod on catecholamines and on the side effects of Nif, Cod may be preferable to other antihypertensives in augmenting the antihypertensive action of Nif.

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

  1. Abisch E, Humbert H (1983) Die Pharmakokinetik von Hyderginspecial, in: Bock KD (ed) Hochdrucktherapie im Alter mit Hydergin: Neue Gesichtspunkte, Nürnberger Expertengespräch. Schattauer, Stuttgart, p 71

    Google Scholar 

  2. Agabiti-Rosei E, Muiesan ML, Romanelli G, Beschi M, Castellano M, Muiesan G (1988) Reversal of cardiac hypertrophy by long-term treatment with calcium antagonists in hypertensive patients. J Cardiovasc Pharmacol 12 [Suppl 6]: S75-S78

    Google Scholar 

  3. Amery A, Brixko P, Clement D, De Schaepdryver A, Fagard R, Forte J, Henry JF, Leonetti G, O'Malley K, Strasser T, Birkenhäger W, Bulpitt M, Deruyttere M, Dollery C, Forette F, Hamdy R, Joossens JV, Lund-Hohansen P, Petrie J, Tuomilehto J, Williams B (1985) Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial. Lancet I: 1349–1370

    Google Scholar 

  4. Ames RP (1986) The effects of antihypertensive drugs on serum lipids and lipoproteins. Drugs 32: 260–278, 335–337

    Google Scholar 

  5. Brouwer RM, Bolli P, Erne P, Conen D, Kiowski W, Bühler R (1985) Antihypertensive treatment using calcium antagonists in combination with captopril rather than diuretics. J Cardiovasc Pharmacol 7 [Suppl 1]: 88–91

    Google Scholar 

  6. Clark BJ, Bucher T, Waite R (1985) Analysis of cardiovascular effects of co-dergocrine (Hydergine). J Pharmacol 16 [Suppl III]: 101–111

    Google Scholar 

  7. Daniels AR, Opie LH (1986) Atenolol plus nifedipine for mild to moderate systemic hypertension after fixed doses of either agent alone. Am J Cardiol 57: 965–970

    Google Scholar 

  8. Daul A, Bock KD, Wang XL, Brodde OE (1985) Effects of nifedipine and co-dergocrine mesylate (Hydergine) on alpha2- and β2-adrenoceptors in circulating blood cells of essential hypertensive patients. Hochdruck 6: 48

    Google Scholar 

  9. Davis JO, Freeman RH (1976) Mechanisms regulating renin release. Physiol Revs 56: 1–56

    Google Scholar 

  10. Gordon RD, Wolf LK, Island DP, Liddle GW (1966) A diurnal rhythm in plasma renin activity in man. J Clin Invest 45: 1587–1592

    Google Scholar 

  11. Guazzi MD, Fiorentini C, Olivari MT, Bartorelli A, Necchi G, Polese A (1980) Short- and long-term efficacy of a calcium antagonistic agent (nifedipine) combined with methyldopa in the treatment of severe hypertension. Circulation 61: 913–919

    Google Scholar 

  12. Hiramatsu K, Yamagishi F, Kubota T, Yamada T (1982) Acute effects of the calcium antagonist, nifedipine, on blood pressure, pulse rate, and the renin-angiotensin-aldosterone system in patients with essential hypertension. Am Heart J 104: 1346–1350

    Google Scholar 

  13. Kiowski W, Hulthen UL, Erne B, Bolli P, Bühler FR (1983) Antihypertensive Wirkung und Wirkmechanismus von Kalziumantagonisten bei essentieller Hypertonie. Therapiewoche 33: 1869–1878

    Google Scholar 

  14. Klein W, Brandt D, Vrecko K, Härringer M (1983) Role of calcium antagonists in the treatment of essential hypertension. Circ Res 52 [Suppl 1]: 174–181

    Google Scholar 

  15. Konsunen KJ (1977) Plasma renin activity, angiotensin II and aldosterone after mental arithmetic. Scand J Clin Lab Invest 37: 425–429

    Google Scholar 

  16. Konsunen KJ, Pakarinen AJ (1976) Plasma renin, angiotensin II and plasma and urinary aldosterone in running exercise. J Appl Physiol 41: 26–29

    Google Scholar 

  17. Lederballe Pedersen O, Mikkelsen E, Christensen NJ, Kornerup HJ, Pedersen EB (1979) Effect of nifedipine on plasma renin, aldosterone and catecholamines in arterial hypertension. Eur J Clin Pharmacol 15: 235–240

    Google Scholar 

  18. Lejeune PH, Gunselmann W, Hennies L (1985) Effects of BAY J 5240, a fixed combination of low-dose nifedipine and acebutolol on essential hypertension: Comparison with standard dose nifedipine. Eur J Clin Pharmacol 27: 17–21

    Google Scholar 

  19. Leren P, Foss OP, Helgeland A, Hjermann I, Holme I, Lund-Larsen PG (1980) Effect of propranolol and prazosin on blood lipids. The Oslo Study. Lancet II: 4–6

    Google Scholar 

  20. Muiesan G, Agabiti-Rosei E, Castellano M, Alicandri CL, Corea L, Fariello R, Beschi M, Romanelli G (1982) Antihypertensive and humoral effects of verapamil and nifedipine in essential hypertension. J Cardiovasc Pharmacol 4 [Suppl 3]: 325–329

    Google Scholar 

  21. Os I, Kjeldsen SE, Westheim A, Normann N, Aakesson I, Hjermann I, Eide I (1987) Central Dopaminergic Control of Prolactin in Essential Hypertension Acta Med Scand 221 [Suppl 714]: 113–117

    Google Scholar 

  22. Petersen K-G, Ortgiese G, Schuler G, Khalaf N, Schliebs B, Kerp L (1989) Glukosetoleranz und Elektrolytstoffwechsel unter Nifedipin and Nifedipin-Dihydroergotoxin bei Gesunden. Arzneim-Forsch/Drug Res 39: 612–614

    Google Scholar 

  23. Rämsch K-D (1983) Pharmakokinetic verschiedener Darreichungsformen von Adalat. In: Just HJ (ed) Erfahrungen mit Adalat in Klinik und Praxis: Prüfergespräch am 23. 10. 1982 in München. Perimed, Erlangen, pp 19–26

    Google Scholar 

  24. Schoenberger JA (1988) Calcium-antagonists: Use in hypertension: Evaluation of calcium-antagonists in combination with diuretics. Angiology 39: 87–93

    Google Scholar 

  25. Sluiter HE, Huysmans FThM, Thien ThA, Koene RAP (1985) The influence of alpha1-adrenergic blockade on the acute antihypertensive effect of nifedipine. Eur J Clin Pharmacol 29: 263–267

    Google Scholar 

  26. Stella A, Zanchetti A (1984) Neural control of renin secretion. J Hypertension 2 [Suppl 1]: 83–87

    Google Scholar 

  27. Stumpe KO, Kolloch R, Higuchi M, Kruck F, Vetter H (1977) Hyperprolactinemia and antihypertensive altered central dopaminergic activity of prolactin in essential hypertension: Effect of bromocriptine in essential hypertension. Lancet II: 211–214

    Google Scholar 

  28. Thames MD (1984) Renin Release: Reflex control and adrenergic mechanisms. J Hypert 2 [Suppl 1]: 57–66

    Google Scholar 

  29. Weidmann PA, Gerber A, Mordasini R (1983) Effects of antihypertensive therapy on serum lipoproteins. Hypertension 5 [Suppl 3]: 120–131

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, University of Frankfurt, Frankfurt am Main

    R. Kirsten & K. Nelson

  2. Clinical Research, Sandoz AG, Nürnberg, FRG

    G. Weidinger & D. Welzel

  3. Abteilung Klinische Pharmakologie - Haus 74, Johann Wolfgang von Goethe Universität, Theodor-Stern-Kai 7, W-6000, Frankfurt am Main 70, FRG

    R. Kirsten

Authors
  1. R. Kirsten
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Weidinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Welzel
    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

Kirsten, R., Nelson, K., Weidinger, G. et al. Co-dergocrine mesylate inhibits the increase in plasma catecholamines caused by nifedipine in essential hypertension. Eur J Clin Pharmacol 39, 435–439 (1990). https://doi.org/10.1007/BF00280932

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00280932

Key words

Search

Navigation