Acta Scientific Nutritional Health (ISSN: 2582-1423)

Short Communication Volume 4 Issue 1

Utilization of a Pyrrolidin-2-One Based Nonselective α-Adrenoceptor Antagonist for Metabolic Syndrome (MetS) Therapy Along with Histamine H3 Inverse Agonist Pitolistant in High Fat Diet Induced Obesity in Mice and Future Role in Humanbeing

Kulvinder Kochar Kaur1*, Gautam Allahbadia2 and Mandeep Singh3

1Scientific Director, Dr Kulvinder Kaur Centre for Human Reproduction, Jalandhar, Punjab, India

2Scientific Director, Rotunda-A Centre for Human Reproduction, Mumbai, India

3Consultant Neurologist, Swami Satyanand Hospital, Jalandhar, Punjab, India

*Corresponding Author: Kulvinder Kochar Kaur, Scientific Director, Dr Kulvinder Kaur Centre for Human Reproduction, Jalandhar, Punjab, India.

Received: October 14, 2019; Published: December 05, 2019

×

  The metabolic syndrome (MetS) by definition is the presence of 3/5 symptoms at the same time, like abnormal fasting glycae-mia, abdominal obesity, increasedblood pressure (BP), hypertrigy-ceridaemia and low amounts of high density lipoprotein ( HDL) [1]. With MetS chances of acquiring serious problems like type2 diabetes mellitus (T2DM), coronary heart disease (CHD), Ischemic stroke and atherosclerosis is present. Statistics conducted recently display that MetS takes place in 20-25% of adult population which has taken epidemic levels [2]. With it becoming a big therapeutic problem in developed countries, emphasis is being laid on produc-ing efficacious, safe cures.

  Earlier researchers had displayed that an enhanced activation of sympathetic nervous system ( SNS) correlates with various parts of MetS. Like the adrenergic nervous system has a crucial role in inducing along with increments of BP, changes in the car-diac output, peripheral vascular resistance along with regulating triglyceride and glucose metabolism [3]. Sympathetic nerve activa-tion has been documented to be much > in patients with MetS, in contrast to healthy subjects [4]. Further on concomitant presence of obesity and hypertension > sympathetic nerve activation is ob-served in MetS subjects as compared to patients presenting with a single disease [5]. Thus inhibiting adrenergic nervous system be-comes a proper method of curing MetS components [6].

×

References

  1. Grundy SM., et al. “Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung and Blood Institute Scientific Statement”. Circulation 112 (2005): 2735-2752.
  2. Zimmert P., et al. “Global and societal implications of the diabetes epidemic”. Nature 414 (2001): 782-787.
  3. Grassi G. “Sympathetic overdrive and cardiovascular risk in the metabolic syndrome”. Hypertension Research 29 (2006): 11.
  4. Grassi G., et al. “Noradrenergic and reflex abnormalities in pts with metabolic syndrome”. Diabetologia 48 (2005): 1359-1365.
  5. Grassi G., et al. “Adrenergic reflex abnormalities in obesity related hypertension”. Hypertension 36 (2000): 538-542.
  6. Thorpe AA and Schlaich MP. “Relevance of sympathetic nervous system activation in obesity and metabolic syndrome”. Journal of Diabetes Research (2015).
  7. Kabra NK. “Alpha blockers and metabolic syndrome”. The Journal of the Association of Physicians of India 52 (2014): 13-16.
  8. Zareba P., et al. “α-adrenoceptor antagonists and hypertensive properties of novel arylpiperazine derivatives of pyrrolidin -2-one”. Bioorganic and Medicinal Chemistry 348 (2015): 2104-2111.
  9. Pessina AC., et al. “Clinical efficacy and tolerability of alpha-blocker doxazosin as add on therapy in patients with hypertension and impaired glucose metabolism”. Nutrition, Metabolism and Cardiovascular Diseases 16 (2006): 137-147.
  10. Lafontan M., et al. “Alpha-2 adrenoceptors and lipid metabolizing in lipolysis”. The American Journal of Clinical Nutrition 55 (2013): 219-225.
  11. Yang SN., et al. “Subthreshold α2-adrenergic activation counteracts glucagon like peptide1 potentiation of glucose stilulated insulin secretion”. Experimental Diabetes Research (2011).
  12. Sarpa J., et al. “Evaluation of anticonvulsant activity of novel pyrrolidin -2-one derivatives”. Pharmacological Reports 66 (2014): 708-711.
  13. Sarpa J., et al. “Antiarrythmic and antioxidant activity of novel pyrrolidin -2-one derivatives with adrenolytic properties”. Naunyn-Schmiedeberg's Archives of Pharmacology 383 (2011): 13-25.
  14. Zareba P., et al. “Antiarrythmic and α-adrenoceptor antagonists properties of novel pyrrolidin -2-one derivatives”. Archives of Pharmacal Research (Weinheim) 348 (2015): 861-7.
  15. Dudek M., et al. “Pyrrolidin -2-one derivatives may reduce body weight in rats with diet induced obesity”. European Journal of Pharmacology 776 (2016): 146-155.
  16. Kotanska M., et al. “Metabolic benefits of 1-(3-(4-(o--(o-tolyl)piperazin-1-yl)-propyl) pyrrolidin -2-one: a nonselective α-adrenoceptor antagonists”. Journal of Endocrinological Investigation t 41 (2018): 609-619.
  17. Walter J and Stark H. “Histamine receptor subtypes: a century of national drug design”. Frontiers in Bioscience S4 (2012): 461-488.
  18. Provensi G., et al. “The Histaminergic system as a target for the prevention of obesity and metabolic syndrome”. Neuropharmacology 106 (2016): 3-12.
  19. Feuerstein TJ. “Presynaptic receptors for dopamine, Histamine and serotonin pharmacology of neurotransmitter release”. Handbook of Experimental pharmacology. 184, Springer-Verlag, Berlin, Heidelberg (2008): 289-338.
  20. Passani MB., et al. “The Histamine H3 receptor and eating behaviour”. Journal of Pharmacology and Experimental Therapeutics 336 (2011): 24-29.
  21. Wang KY., et al. “Histamine regulation of lipid and glucose metabolism via Histamine receptors”. The American Journal of Pathology 177 (2010): 713-722.
  22. Mamelof K., et al. “Increase of neuronal Histamine in obese rats is associated with decreases in body weight and plasma triglycerides”. Obesity 14 (2006): 2154-2162.
  23. Nakamura T., et al. “The expression and function of Histamine H3 receptors in pancreatic beta cells”. British Journal of Pharmacology 171 (2014): 171-185.
  24. Barbier AJ., et al. “Acute wake promoting actions of JNJ-5207852, a novel, diamine –based H3 antagonist”. British Journal of Pharmacology 143 (2004): 649-661.
  25. Barak N., et al. “Effect of histaminergic manipulation on weight on weight in obese adults: a randomized controlled trial”. International Journal of Obesity 32 (2008): 1559-1565.
  26. Lian J., et al. “Preventing olanzapine –induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment”. PLoS One8 (2014): e104160.
  27. European Medicines Agency.
  28. Kotanska M., et al. “The Histamine H3 receptor inverse agonist pitolisant reduces body weight in obese mice”. Naunyn-Schmiedeberg's Archives of Pharmacology 391 (2018): 875-881.
×

Citation

Citation: Kulvinder Kochar Kaur., et al. "Utilization of a Pyrrolidin-2-One Based Nonselective α-Adrenoceptor Antagonist for Metabolic Syndrome (MetS) Therapy Along with Histamine H3 Inverse Agonist Pitolistant in High Fat Diet Induced Obesity in Mice and Future Role in Humanbeing".Acta Scientific Nutritional Health 4.1 (2020): 30-33.



Member In




News and Events


  • Submission Timeline for Regular Issue
    The last date for submission of articles for regular Issues is January 30, 2020.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of “Best Article of the Issue”.
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.
  • Contact US