Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors

Authors

  • Eldina Rizvić Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
  • Goran Janković Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
  • Slađana Kostić-Rajačić Institute of Chemistry, Technology and Metallurgy (ICTM), University of Belgrade, Belgrade, Serbia
  • Miroslav M. Savić Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia

DOI:

https://doi.org/10.17305/bjbms.2017.2071

Keywords:

Lerimazoline, rat aorta, binding affinity, phenylephrine, 5-HT2A receptors, St-71, trimizoline, tramazoline, antagonist activity, sympathomimetic drug

Abstract

Lerimazoline is a sympathomimetic drug that belongs to the imidazoline class of compounds, and is used as a nasal decongestant. Studies on lerimazoline are rare, and its pharmacological profile is not completely understood. Here, we analyzed the affinity of lerimazoline for dopamine receptor D2, serotonin 5-HT1A and 5-HT2A receptors and α1-adrenoceptor, and investigated lerimazoline contractile effects in isolated rat thoracic aorta. We also determined the effect of several antagonists on the contractile response to lerimazoline, including prazosin (α1-adrenoceptor antagonist), RX 821002 and rauwolscine (α2-adrenoceptor antagonists), JP 1302 (α2C-adrenoceptor antagonist), methiothepin (non-selective 5-HT receptor antagonist), SB 224289 (5-HT1B receptor antagonist), BRL 15572 (5-HT1D receptor antagonist), and ketanserin (5-HT2A receptor antagonist). Lerimazoline displayed high affinity for the 5-HT1A receptor (Ki = 162.5 nM), similar to the previously reported affinity for the 5-HT1D receptor. Binding affinity estimates (Ki) for α1, 5-HT2A, and D2 receptors were 6656, 4202 and 3437.5 nM, respectively (the literature reported Ki for 5-HT1B receptor is 3480 nM). Lerimazoline caused concentration-dependent contractions in 70% of preparations, varying in the range between 40% and 55% of the maximal contraction elicited by phenylephrine. While prazosin reduced the maximum contractile response to lerimazoline, rauwolscine showed a non-significant trend in reduction of the response. Both ketanserin (10 nM and 1 µM) and methiothepin strongly suppressed the maximum response to lerimazoline. Overall, our results suggest that 5-HT2A and, less distinctly, α1-adrenergic receptors are involved in the lerimazoline-induced contractions, which makes lerimazoline an “atypical” decongestant.

Author Biographies

  • Eldina Rizvić, Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
    Department of Pharmacology
  • Goran Janković, Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
    Department of Pharmacology
  • Miroslav M. Savić, Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
    Department of Pharmacology

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Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors

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Published

20-08-2017

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1.
Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors. Biomol Biomed [Internet]. 2017 Aug. 20 [cited 2024 Mar. 19];17(3):194-202. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/2071