Skip to main content
Log in

Risperidone Inhibits Contractions Induced by Serotonin and Histamine and Reduces K+ Currents in Smooth Muscle of Human Umbilical Artery

  • Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Risperidone is an antipsychotic commonly used during pregnancy. Because it can cross the placental barrier, our objective was to evaluate its actions on the smooth muscle of the human umbilical artery (HUA). Risperidone preincubation (1–300 nmol/L for 20 minutes) produced a significant decrease in maximum force development induced by serotonin or histamine in HUA rings. When applied on top of stable contractions induced by these agonists risperidone produced quick relaxations (IC50 = 1 nmol/L for serotonin and 72 nmol/L for histamine). Risperidone induced the contraction of vascular rings depolarized by 40 mmol/L extracellular K+ but not in the case of 80 mmol/L K+, suggesting inhibition of K+ channels. The patch-clamp technique showed that risperidone (3 nmol/L) inhibited whole-cell K+ currents in freshly isolated HUA smooth muscle cells. Our results are the first showing risperidone effects in human vascular smooth muscle and highlight that its use during pregnancy should be adequately monitored.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Häfner H, Riecher A, Maurer K, Löffler W, Munk-Jørgensen P, Strömgren E. How does gender influence age at first hospitalization for schizophrenia? A transnational case register study. Psychol Med. 1989;19(4):903–918.

    Article  Google Scholar 

  2. Iveli MF, Rebolledo A, Milesi V. Atypical antipsychotic drugs during pregnancy. Its effects on the mother and on the offspring. Curr Womens Health Rev. 2009;5(2):100–108.

    Article  CAS  Google Scholar 

  3. Reis M, Källón B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol. 2008;28(3):279–288.

    Article  CAS  Google Scholar 

  4. Coppola D, Russo LJ, Kwarta RF Jr, Varughese R, Schmider J. Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. Drug Saf. 2007;30(3):247–264.

    Article  CAS  Google Scholar 

  5. McKenna K, Koren G, Tetelbaum M, et al. Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. J Clin Psychiatry. 2005;66(4):444–449.

    Article  CAS  Google Scholar 

  6. American Academy of Pediatrics. Committee on Drugs. Use of psychoactive medication during pregnancy and possible effects on the fetus and newborn. Pediatrics. 2000;105(4 pt 1):880–887.

    Google Scholar 

  7. Newport DJ, Calamaras MR, DeVane CL, et al. Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcomes. Am J Psychiatry. 2007;164(8): 1214–1220.

    Article  Google Scholar 

  8. Grant S, Fitton A. Risperidone: a review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs. 1994;48(2):253–273.

    Article  CAS  Google Scholar 

  9. Bertrand C, St-Louis J. Reactivities to serotonin and histamine in umbilical and placental vessels during the third trimester after normotensive pregnancies and pregnancies complicated by preeclampsia. Am J Obstet Gynecol. 1999;180(3 pt 1):650–659.

    Article  CAS  Google Scholar 

  10. Lovren F, Li XF, Lytton J, Triggle C. Functional characterization and m-RNA expression of 5-HT receptors mediating contraction in human umbilical artery. Br J Pharmacol. 1999;127(5): 1247–1255.

    Article  CAS  Google Scholar 

  11. Gardner DS, Fletcher AJW, Fowden AL, Giussani DA. A novel method for controlled and reversible long term compression of the umbilical cord in fetal sheep. J Physiol. 2001;535(pt 1):217–229.

    Article  CAS  Google Scholar 

  12. Clapp JF, Peress NS, Wesley M, Mann LI. Brain damage after intermittent partial cord occlusion in the chronically instrumented fetal lamb. Am J Obstet Gynecol. 1988;159(2): 504–509.

    Article  CAS  Google Scholar 

  13. Christ T, Wettwer E, Ravens U. Risperidone-induced action potential prolongation is attenuated by increase repolarization reserve due to concomitant block of ICaL. Naunyn Schmiedebergs Arch Pharmacol. 2005;371(5):393–400.

    Article  CAS  Google Scholar 

  14. Gluais P, Bastide M, Caron J, Adamantidis M. Risperidone prolongs cardiac action potential through reduction of K+ currents in rabbit myocytes. Eur J Pharmacol. 2002;444(3): 123–132.

    Article  CAS  Google Scholar 

  15. Magyar J, Banyasz T, Pacher P, et al. Electophysiological effects of risperidone in mammalian cardiac cells. Naunyn Schimiedebergs Arch Pharmacol. 2002;366(4):350–356.

    Article  CAS  Google Scholar 

  16. Klockner U. Intracellular calcium ions activate a low-conductance chloride channel in smooth-muscle cells isolated from human mesenteric artery. Pflügers Arch. 1993;424(3–4): 231–237.

    Article  CAS  Google Scholar 

  17. Milesi V, Raingo J, Rebolledo A, Grassi de Gende AO. Potassium channels in human umbilical artery cells. J Soc Gynecol Investig. 2003;10(6):339–346.

    Article  CAS  Google Scholar 

  18. Hamill OP, Marty A, Neher E, Sackmann B, Sigworth FJ. Improved patch clamp techniques for high-resolution current readings from cells and cell-free membrane patches. Pflügers Arch. 1981;391(2):85–100.

    Article  CAS  Google Scholar 

  19. Olesen OV, Licht RW, Thomsen E, Bruun T, Viftrup JE, Linnet K. Serum concentrations and side effects in psychiatric patients during risperidone therapy. Ther Drug Monit. 1998; 20(4):380–384.

    Article  CAS  Google Scholar 

  20. Kuroki T, Nagao N, Nakahara T. Neuropharmacology of second-generation antipsychotic drugs: a validity of the serotonin-dopamine hypothesis. Prog Brain Res. 2008;172:199–212.

    Article  CAS  Google Scholar 

  21. Sexton AJ, Loesch A, Turmaine M, Miah S, Burnstock G. Electron-microscopic immunolabelling of vasoactive substances in human umbilical endothelial cells and their actions in early and late pregnancy. Cell Tissue Res. 1996;284(1):167–175.

    Article  CAS  Google Scholar 

  22. Lang U, Baker RS, Braems G, Zygmunt M, Künzel W, Clark KE. Uterine blood flow—a determinant of fetal growth. Eur J Obstet Gynecol Reprod Biol. 2003;110(suppl):S55–S61.

    Article  Google Scholar 

  23. Lang U, Baker RS, Khoury J, Clark KE. Effects of chronic reduction in uterine blood flow on fetal and placental growth in the sheep. Am J Physiol Regul Integr Comp Physiol. 2000;279(1): R53–R59.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alejandro Rebolledo PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iveli, M.F., Rebolledo, A., Martín, P. et al. Risperidone Inhibits Contractions Induced by Serotonin and Histamine and Reduces K+ Currents in Smooth Muscle of Human Umbilical Artery. Reprod. Sci. 17, 854–860 (2010). https://doi.org/10.1177/1933719110372420

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719110372420

Keywords

Navigation