Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012, 156(2):122-127 | DOI: 10.5507/bp.2012.028

Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and biodistribution than glibenclamide-OH in alloxan-rats

Lauro Figueroa-Valverdea, Francisco Diaz-Cedillob, Maria Lopez-Ramosa, Elodia Garcia-Cerveraa, Eduardo Pool-Gomeza, Carlos Cardena-Arredondoc, Graciela Ancona-Leona
a Laboratorio de Investigacion en Ciencias Biologicas y Farmacoqimica, Facultad de Ciencias Quimico-Biologicas, Universidad Autonoma de Campeche, Av. Agustin Melgar, Col Buenavista C.P.24039 Campeche Cam., Mexico
b Escuela Nacional de Ciencias Biologicas del Instituto Politecnico Nacional. Prol. Carpio y Plan de Ayala s/n Col. Santo Tomas, D.F. C.P. 11340, Mexico
c Centro Estatal de Oncologia, Campeche Cam., Mexico

Aim: The present study was designed to investigate the activity of two glibenclamide derivatives on glucose concentration. An additional aim was to identify the biodistribution of glibenclamide derivatives in different organs in a diabetic animal model.

Methods: The effects of two glibenclamide derivatives on glucose concentration were evaluated in a diabetic animal model. In addition, glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30, 45 and 60 min) the Tc-99m-glibenclamide conjugates were used.

Results: The results showed that glibenclamide-pregnenolone had greater hypoglycemic activity than glibenclamide or glibenclamide-OH. The data also showed that the biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of the Tc-99m-glibenclamide-pregnenolone derivative.

Conclusions: The glibenclamide-pregnenolone derivative had greater hypoglycemic effects and its biodistribution was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be important to the hypoglycemic activity of the glibenclamide-pregnenolone derivative and this could be related to the degree of lipophilicity induced by the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.

Keywords: glibenclamide, pregnenolone, biodistribution, glucose

Received: May 23, 2011; Accepted: February 24, 2012; Prepublished online: April 19, 2012; Published: June 1, 2012  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Figueroa-Valverde, L., Diaz-Cedillo, F., Lopez-Ramos, M., Garcia-Cervera, E., Pool-Gomez, E., Cardena-Arredondo, C., & Ancona-Leon, G. (2012). Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and biodistribution than glibenclamide-OH in alloxan-rats. Biomedical papers, 156(2), 122-127. doi: 10.5507/bp.2012.028
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Kelsey I, Wright P. The action of hypoglycaemic sulphonylureas on carbohydrate metabolism in the fasted rat. Br J Pharmacol Chemother 1957;12(3):350-5. Go to original source... Go to PubMed...
    2. Cerasi E, Efendic S, Thornqvist C, Luft R. Effect of two sulphonylureas on the dose kinetics of glucose-induced insulin release in normal and diabetic subjects. Acta Endocrinol (Copenh) 1979;91(2):282-93. Go to original source... Go to PubMed...
    3. Graal MB, Wolffenbuttel BH. The use of sulphonylureas in the elderly. Drugs Aging 1999;15(6):471-81. Go to original source... Go to PubMed...
    4. Beck-Nielsen H, Pedersen O, Lindskov HO. Increased insulin sensitivity and cellular insulin binding in obese diabetics following treatment with glibenclamide. Acta Endocrinol (Copenh) 1979;90(3):451-62. Go to original source... Go to PubMed...
    5. Chan J, Tomlinson B, Critchley J, Cockram C, Walden R. Metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. Diabetes Care 1993;16(7):1035-38. Go to original source... Go to PubMed...
    6. Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with ascarbose, glibenclamide, or placebo in NIDDM patients. The Essen Study. Diabetes Care 1994;17(6):561-6. Go to original source... Go to PubMed...
    7. Asplund K, Wiholm B, Lithner F. Glibenclamide-associated hypoglycaemia: a report on 57 cases. Diabetologia 1983;24:412-17. Go to original source... Go to PubMed...
    8. Ferner RE, Neil HA. Sulphonylureas and hypoglycaemia. Br Med J 1988;296:959-60. Go to original source... Go to PubMed...
    9. Pearson JC, Antal EJ, Rachl GL, Gorsch HK, Craig WA, Albert KA, Welling PG. Pharmacokinetic disposition of 14C- glyburide in patients with varying renal function. Clin Pharmac Ther 1986;39:318- 24. Go to original source... Go to PubMed...
    10. Ferner RE, Chaplin S. The relationship between the pharmacokinetics and pharmacodynamics effects of oral hypoglycaemic drugs. ClinPharmacokin 1987;12:379-401. Go to original source... Go to PubMed...
    11. Garrino M, Schmeer W, Nenquin M, Meissner H, Henquin J. Mechanism of the stimulation of insulin release in vitro by HB 699, a benzoic acid derivative similar to the non-sulphonylurea moiety of glibenclamide. Diabetologia 1985;28:697-703. Go to original source... Go to PubMed...
    12. Holstein A, Plaschke A, Hammer C, Egberts E. Characteristics and time course of severe glimepiride- versus glibenclamide-induced hypoglycaemia. Eur J Clin Pharmacol 2003;59:91-7 Go to original source... Go to PubMed...
    13. Holstein A, Plaschke A, Egberts E. Lower incidence of severe hypoglycaemic in patients with type 2 diabetes treated with glimepiride versus glibenclamide. Diabetes/Metabolism Res Rev 2001;17(6):467- 73. Go to original source... Go to PubMed...
    14. Balant L, Fabre J, Zahnd G. Comparison of the Pharmacokinetics of Glipizide and Glibenclamide in Man. Eur J Clin Pharmacol 1975;8:63- 9. Go to original source... Go to PubMed...
    15. Groop L, Wfihlin-Boll E, Groop R, Totterman K, Melander A, Tolppanen E, Fyhrqvist F. Pharmacokinetics and Metabolic Effects of Glibenclamide and Glipizide in Type2 Diabetics. Eur J Clin Pharmacol 1985;28:697-704. Go to original source... Go to PubMed...
    16. Jayo M, Cisneros F. Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, National Academy Press Washington, D.C 1996.
    17. Figueroa-Valverde L, Diaz-Cedillo F, Garcia-Cervera. Synthesis of Glibenclamide-pregnenolone conjugate and its relationship with physicochemical descriptors log P, , Rm, Vm, Pc and St. Asian J Chem 2011;23(9):3999-4002.
    18. Figueroa-Valverde L, Diaz-Cedillo F, Camacho-Luis A, Lopez-Ramos M, Garcia-Cervera E. Design and Synthesis of Carbamazepine-Alkyne Conjugate as Antidiabetic Agent: Study of Chemical Descriptors (log P and ). Asian J Chem 2010;22(9):7057-64.
    19. Kawashima K, Kuzuya T, Matsuda A. Radioimmunoassay of glibenclamide. Diabetes 1979;28(3):221-6. Go to original source... Go to PubMed...
    20. Schneider S, Ueberberg S, Korobeynikov A, Schechinger W, Schwanstecher C, Schwanstecher M, Klein H,Schirrmacher E. Synthesis and evaluation of a glibenclamide glucose-conjugate: A potential new lead compound for substituted glibenclamide derivatives as islet imaging agents. Regulatory Peptides 2007;139(1-3):122- 7. Go to original source... Go to PubMed...
    21. Yoda R, Arube Y, Takata J, Nagata Y, Matsushima Y. Technetium- 99m Complexes with Steroid-2-aminooxyethyliminodiaceticAcid Conjugates. Chem Pharm Bull 1999;47(3):413-6. Go to original source... Go to PubMed...
    22. Yumisley A, Rivero A , Zayas F, Mesa N, Hernandez I , Leon M. Formulacion de 99M TC-Macroagregadosde albumina para estudios de perfusion pulmonar. Nucleus 2009;45:19-25.
    23. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 2001:50:536-46.
    24. Seedher N, Kanojia M. Mechanism of interaction of hypoglycemic agents glimepiride and glipizide with human serum albumin. Central Eur J Chem 2009;7(1):96-104. Go to original source...
    25. Fu J, Gaetani S, Oveisi F, Verme J, Serrano A, Rodríguez F, Rosengarth A, Luecke H, Di Giacomo B, Tarzia G, Piomelli D. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-. Nature 2003;425:90-3. Go to original source... Go to PubMed...

    Return to the content