Investigation of the role of i1- and i2-imidazoline receptors in the mechanіsm of the hypoglycemic action of n,n’-(ethane-1,2 dyyil)bis(quinoline- 2-carboxamide)

Authors

  • O. M. Kalapko National University of Pharmacy, Ukraine
  • S. Yu. Shtrygol’ National University of Pharmacy, Ukraine
  • S. Yu. Shtrygol’ National University of Pharmacy, Ukraine
  • B. V. Paponov V.N.Karazin Kharkiv National University, Ukraine
  • B. V. Paponov V.N.Karazin Kharkiv National University, Ukraine
  • S. V. L’vov V.N.Karazin Kharkiv National University, Ukraine
  • S. V. L’vov V.N.Karazin Kharkiv National University, Ukraine

DOI:

https://doi.org/10.24959/nphj.14.1970

Keywords:

N, N’-(ethane-1, 2-dyyil)bis(quinoline-2-carboxamide), hypoglycemic effect, imidazoline receptors, diabetes mellitus, 2-(4, 5-dihydroimidazol-2-yl)quinoline hydrochloride (BU 224), efaroxan, alloxan

Abstract

The results of the investigation of the hypoglycemic action mechanism of N,N’-(ethane-1,2-dyyil)bis (quinoline-2-carboxamide) are presented. The substance was administered intragastrically in the dose of 11.64 mg/kg on the model of alloxan-induced diabetes mellitus in rats. It should be noted that the test compound in terms of the theory of pharmacophore can be considered as a dimer BU 224, but it is not its dimer in terms of organic chemistry. The information about the influence of the test compound on carbohydrate metabolism is limited. There are data that this compound has antitumor properties іn vitro due to enhanced apoptosis and activation of caspase-3. Proceeding from the chemical structure, the 2-substituted quinoline fragment is present in the structure of the known antagonist of imidazoline receptors I2 such as 2-(4,5-dihydroimidazol-2-yl)quinoline hydrochloride, so it can be assumed that N,N’-(ethane-1,2-dyyil)bis(quinoline-2-carboxamide) has the ability to interfere with the mechanisms of the carbohydrate metabolism regulation. These results indicate that N,N’-(ethane- 1,2-dyyil)bis(quinolin-2-carboxamide) has an expressed hypoglycemic effect in alloxan-induced diabetes mellitus reducing the blood glucose level by 71.50%. It is an agonist of imidazoline receptors of both types, and it has been proven by blockade with selective antagonists such as efaroxan and 2-(4,5-dihydroimidazol-2-yl)quinoline hydrochloride. On the background of I1-imidazoline receptors blocker efaroxan the glycemia decrease was 45.66% (p<0.05), and on the background of I2-imidazoline receptors blocker 2-(4,5-dihydroimidazol-2-yl)quinoline hydrochloride it was 54.01% (p<0.05).

References

Балаболкин М.И. Диабетология. – М.: Медицина, 2000. – 471 с.

Козаева Л.П., Коробов Н.В., Медведев О.С. // Эксперимент. и клин. фармакол. – 2003. – Т. 66, №5. – С. 69-73.

Миронов А.Н. Руководство по проведению доклинических исследований лекарственных средств. – М.: Гриф и К, 2012. – Ч. I. – 944 с.

Стефанова О.В. Доклінічні дослідження лікарських засобів: Метод. рекоменд. – К.: Авіценна, 2001. – 400 с.

American Diabetes Association // Diabetes Care. – 2006. – Vol. 29. – P. 1-42.

Cheng C.H., Tsao C.W., Huang S.Y. et al. // Neorosci. Lett. – 2009. – Vol. 467. – Р. 147-149.

Cheng J.T., Huang C.C., Liu I.M. et al. // Diabetes. – 2006. – Vol. 55. – P. 819-825.

Dave K.R., Katyare S.S. // J. оf Endocrinol. – 2002. – Vol. 175, №1. – Р. 241-250.

Echeverria M., Mendivil B., Cordeuetal L. // Arch. Pharm. Chem. Life Sci. – 2006. – Vol. 339. – P. 182-192.

Ernsberger P. // Ann. NY Acad. Sci. – 1999. – Vol. 881. – P. 35-53.

Harron D. // N. Fundam. Clin. Pharmacol. – 1992. – Vol. 6. – P. 41-44.

Huang S., Zhong R., Liang M. // China J. Mod. Med. – 2004. – Vol. 14, №17. – P. 34-36.

Kalapko O.N., Shtrygol’ S.Yu. // The XXI Intern. Sci. and Pract. Conf. of young Scientists and students “Actual questions of development of new drugs” April 22, 2014, Kharkiv.

Kekalainen P., Sarlund H., Pyorala K. // Diabetes Care. – 1999. – Vol. 22, №1. – P. 86-92.

Lebovitz H.Е., Austin M.M., Blonde L. et al. // Endocrin. Pract. – 2006. – Vol. 12 (Suppl. 1). – P. 6-12.

Lee J.P., Chen W., Wu H.T. et al. // Horm. Metab. Res. – 2011. – Vol. 43, №1. – P. 26-30.

Ong K.L., Cheung B.M., Wong L.Y. et al. // Ann. Epidemiol. – 2009. – Vol. 18. – P. 222-229.

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Published

2014-09-12

Issue

Section

Experimental and Clinical Pharmacology