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

  • 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
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.

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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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Published
2017-08-20
How to Cite
1.
Rizvić E, Janković G, Kostić-Rajačić S, Savić MM. Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors. Bosn J of Basic Med Sci [Internet]. 2017Aug.20 [cited 2019Nov.14];17(3):194-02. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/2071
Section
Biochemistry