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.
Highlights
Several sympathomimetic drugs are used as topical nasal decongestants
To examine the involvement of noradrenergic (α1- and α2-adrenoceptor) and serotonergic systems in lerimazoline-induced contraction, selective α-adrenoceptor and serotonergic antagonists were used in the rat aortas (Table 3)
Prazosin caused a rightward shift in the concentration-response curve to lerimazoline, we were not able to calculate the pKb value because DR was less than 1
Summary
Several sympathomimetic drugs are used as topical nasal decongestants. These drugs are commonly classified into sympathomimetic amines (e.g., phenylephrine and ephedrine) and imidazolines (e.g., oxymetazoline and xylometazoline). Topical decongestants are short-term effective in relieving nasal congestion, a prominent symptom associated with conditions such as common cold, allergic rhinitis, sinusitis or otitis media [1]. Submitted: 26 March 2017/Accepted: 12 May 2017 use there is a risk of development of rebound congestion or rhinitis medicamentosa [2] The risk of such a serious complication may be prevented or at least delayed using a polypharmacological, as opposed to single-target approach, aimed to optimize the therapeutic outcome by concomitant modulation of multiple rather than single drug targets [3,4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
