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

摘要

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-HT 1A and 5-HT 2A receptors and α 1 -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 (α 1 -adrenoceptor antagonist), RX 821002 and rauwolscine (α 2 -adrenoceptor antagonists), JP 1302 (α 2C -adrenoceptor antagonist), methiothepin (non-selective 5-HT receptor antagonist), SB 224289 (5-HT 1B receptor antagonist), BRL 15572 (5-HT 1D receptor antagonist), and ketanserin (5-HT 2A receptor antagonist). Lerimazoline displayed high affinity for the 5-HT 1A receptor (Ki = 162.5 nM), similar to the previously reported affinity for the 5-HT 1D receptor. Binding affinity estimates (Ki) for α 1 , 5-HT 2A , and D 2 receptors were 6656, 4202 and 3437.5 nM, respectively (the literature reported Ki for 5-HT 1B 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-HT 2A and, less distinctly, α 1 -adrenergic receptors are involved in the lerimazoline-induced contractions, which makes lerimazoline an “atypical” decongestant.