TY  - JOUR
AU  - Rizvić, Eldina
AU  - Janković, Goran
AU  - Savić, Miroslav
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2993
AB  - Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline (10(-6) M and especially 10(-7) M) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations (10(-4) M and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor N-W-nitro-L-arginine methyl ester (L-NAME; 10(-4)M) or NO scavanger OHB12 (10(-3)M), as well as non-specific inhibition of K+-channels with tetraethylammonium (TEA; 10(-3) M), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin (10(-5) M) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at 3x10(-7) and 10(-6) M, but not at the highest concentration (10(-4) M). Neither the 5-HT1D-receptor selective antagonist BRL 15572 (10(-6) M) nor 5-HT7 receptor selective antagonist SB 269970 (10(-6) M) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and K+-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-HT2B subtype.
PB  - Korean Journal Of Physiology & Pharmacology, Seoul
T2  - Korean Journal of Physiology & Pharmacology
T1  - Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant
VL  - 21
IS  - 4
SP  - 385
EP  - 395
DO  - 10.4196/kjpp.2017.21.4.385
ER  - 

@article{
author = "Rizvić, Eldina and Janković, Goran and Savić, Miroslav",
year = "2017",
abstract = "Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline (10(-6) M and especially 10(-7) M) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations (10(-4) M and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor N-W-nitro-L-arginine methyl ester (L-NAME; 10(-4)M) or NO scavanger OHB12 (10(-3)M), as well as non-specific inhibition of K+-channels with tetraethylammonium (TEA; 10(-3) M), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin (10(-5) M) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at 3x10(-7) and 10(-6) M, but not at the highest concentration (10(-4) M). Neither the 5-HT1D-receptor selective antagonist BRL 15572 (10(-6) M) nor 5-HT7 receptor selective antagonist SB 269970 (10(-6) M) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and K+-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-HT2B subtype.",
publisher = "Korean Journal Of Physiology & Pharmacology, Seoul",
journal = "Korean Journal of Physiology & Pharmacology",
title = "Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant",
volume = "21",
number = "4",
pages = "385-395",
doi = "10.4196/kjpp.2017.21.4.385"
}

Rizvić, E., Janković, G.,& Savić, M.. (2017). Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant. in Korean Journal of Physiology & Pharmacology
Korean Journal Of Physiology & Pharmacology, Seoul., 21(4), 385-395.
https://doi.org/10.4196/kjpp.2017.21.4.385

Rizvić E, Janković G, Savić M. Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant. in Korean Journal of Physiology & Pharmacology. 2017;21(4):385-395.
doi:10.4196/kjpp.2017.21.4.385 .

Rizvić, Eldina, Janković, Goran, Savić, Miroslav, "Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant" in Korean Journal of Physiology & Pharmacology, 21, no. 4 (2017):385-395,
https://doi.org/10.4196/kjpp.2017.21.4.385 . .

TY  - JOUR
AU  - Rizvić, Eldina
AU  - Janković, Goran
AU  - Kostić-Rajacić, Sladana
AU  - Savić, Miroslav
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2790
AB  - 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 alpha(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 (alpha(1)-adrenoceptor antagonist), RX 821002 and rauwolscine (alpha(2)-adrenoceptor antagonists), JP 1302 (alpha(2C)-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 alpha(1), 5-HT2A, and D-2 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 mu M) and methiothepin strongly suppressed the maximum response to lerimazoline. Overall, our results suggest that 5-HT2A and, less distinctly, alpha(1)-adrenergic receptors are involved in the lerimazoline-induced contractions, which makes lerimazoline an "atypical" decongestant.
PB  - Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa
T2  - Bosnian Journal of Basic Medical Sciences
T1  - Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors
VL  - 17
IS  - 3
SP  - 194
EP  - 202
DO  - 10.17305/bjbms.2017.2071
ER  - 

@article{
author = "Rizvić, Eldina and Janković, Goran and Kostić-Rajacić, Sladana and Savić, Miroslav",
year = "2017",
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 alpha(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 (alpha(1)-adrenoceptor antagonist), RX 821002 and rauwolscine (alpha(2)-adrenoceptor antagonists), JP 1302 (alpha(2C)-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 alpha(1), 5-HT2A, and D-2 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 mu M) and methiothepin strongly suppressed the maximum response to lerimazoline. Overall, our results suggest that 5-HT2A and, less distinctly, alpha(1)-adrenergic receptors are involved in the lerimazoline-induced contractions, which makes lerimazoline an "atypical" decongestant.",
publisher = "Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa",
journal = "Bosnian Journal of Basic Medical Sciences",
title = "Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors",
volume = "17",
number = "3",
pages = "194-202",
doi = "10.17305/bjbms.2017.2071"
}

Rizvić, E., Janković, G., Kostić-Rajacić, S.,& Savić, M.. (2017). Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors. in Bosnian Journal of Basic Medical Sciences
Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, Cekalusa., 17(3), 194-202.
https://doi.org/10.17305/bjbms.2017.2071

Rizvić E, Janković G, Kostić-Rajacić S, Savić M. Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors. in Bosnian Journal of Basic Medical Sciences. 2017;17(3):194-202.
doi:10.17305/bjbms.2017.2071 .

Rizvić, Eldina, Janković, Goran, Kostić-Rajacić, Sladana, Savić, Miroslav, "Atypical sympathomimetic drug lerimazoline mediates contractile effects in rat aorta predominantly by 5-HT2A receptors" in Bosnian Journal of Basic Medical Sciences, 17, no. 3 (2017):194-202,
https://doi.org/10.17305/bjbms.2017.2071 . .