ANTIDEPRESSANT LIKE EFFECT OF NEWLY SYNTHESIZED COMPOUND 2[(N- BENZYLACETAMIDO) MERCAPTO] BENZIMIDAZOLE (VS 25) AND ITS POSSIBLE MECHANISM BY INHIBITION OF MONOAMINE OXIDASE ENZYME IN MICE

Authors

  • Vaishali M. Mute Poona College of Pharmacy,Bharati Vidyapeeth Deemed University,Pune.M.S,India.
  • Subhash L. Bodhankar Bharati Vidyapeeth Deemed University

Keywords:

Forced swim test, Monoamine oxidase enzyme Inhibition, Moclobemide, VS25

Abstract

Objective: The objective of the study was to investigate the antidepressant activity of a newly synthesized compound 2 [(N-benzylacetamido) mercapto] benzimidazole (VS 25) by forced swimming test in mouse and to explore the mechanism of action by its effect on monoamine oxidase enzyme in mouse brain.

Methods: Swiss albino mice were randomly divided into 4 groups, each containing 6 animals. Group one was controlled and received 1 % cmc, p. o., Group II received moclobemide (50 mg/kg) p. o., group three and four received VS25 (30mg/kg and 60 mg/kg) once a day for 14 days.

Results: In the forced swim test the decrease in immobility was 38.10% in moclobemide treated mice compared to 34.66% in VS25 (30 mg/kg) and 28.77% in VS 25 (60 mg/kg) treated mice. The percentage inhibition of the monoamine oxidase enzyme in mouse brain mitochondria was in moclobemide treated animals was 75.19% compared to 66.94% in VS 25 (30mg/kg) and 55.52% in VS 25 (60 mg/kg) treated animals. Moclobemide did not inhibit MAO B enzyme while VS25 (30 mg/kg) showed 6.48% and VS 25 (60 mg/kg) showed 4.75% inhibition.

Conclusion: It is concluded that both moclobemide (50 mg/kg) and VS25 (30 mg/kg) showed antidepressant activity in mice. Moclobemide selectively inhibited MAO A enzyme in mouse brain. VS 25 (30 mg/kg) was equipotent as MAO A inhibitor but differed from moclobemide with respect to weak inhibition of MAO B activity also.

 

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Author Biography

Vaishali M. Mute, Poona College of Pharmacy,Bharati Vidyapeeth Deemed University,Pune.M.S,India.

Pharmacology

References

Geneva. The World Health report. An overview of a strategy to improve the mental health of underserved populations. WHO; 1999. p. 5.

Lipson S, Chad E, Beyer, Zoe A, Hughes, Kawaka X, et al. Differentiating antidepressants of the future: efficacy and safety. Pharmacol Ther 2007;113:134-53.

McKinney WT. Animal models of depression: an overview. Psychiatry 1984;2:77-96.

Willner P. Validity, reliability and utility of chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacol 1997;134:319-29.

Luo L. Antidepressant effects of banxia houpu decoction, a traditional Chinese medicinal empirical formula. J Ethnopharmacol 2000;73:277–81.

Chen KX. Quantitative structure–activity relationship analysis of aryl alkanol piperazine derivatives with antidepressant activities. Eur J Med Chem 2009;44:4367–75.

Baker GB, Matveychuk D, MacKenzie EM, Dursun SM, Mousseau DD. Monoamine oxidase inhibitors and neuroprotective mechanisms. Bull Clin Psychopharmacol 2012;22:293-6.

Shelke SM, Bhosale SH, Das RC, Suryawanshi MR, Mahadik K. Exploration of new scaffolds as potent MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening. Bioorg Med Chem Lett 2011:21:2419-24.

Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978;47:379-91.

Porsolt RD, Bertin A, Balavet N, Deniel M, Jalfre M. Immobility induced by forced swimming rats: effect of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol 1979;57:201-10.

Abel EL, Bilitzke PJ. A possible alarm substance in the forced swimming test. Physiol Behav 1990;48:233-9.

Dhingra D, Goyal PK. Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of Tinospora cordifolia in mice. Indian J Pharm Sci 2008;70:761.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951;193:265-75.

Bowers SL, Bilbo SD, Dhabhar FS, Nelson RJ. Stressor-specific alterations in corticosterone and immune responses in mice. Brain Behav Immune 2008;22:105-13.

Cryan JF, Markou A, Irwin L. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 2002;23:238-45.

Iversen L. The Monoamine Hypothesis of Depression. In: Licinio J, Wong ML, editors. Biology of Depression. From Novel Insights to Therapeutic Strategies. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim; 2005. p. 71-86.

Manji HK, Quiroz JA, Sporn J. Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult to treat depression. Biol Psychiatry 2003;53:707–42.

Koelle GB, Valk Ade T. Physiological implications of the histochemical localization of monoamine oxidase. J Physiol 1954;126:434-47.

Davison AN. Physiological role of monoamine oxidase. Physiol Rev 1958;38:729-47.

Krajl Michael. A rapid microfluorimetric determination of monoamine oxidase. Biochem Pharmacol 1965;14:1684-5.

Snyder SH, Hendley ED. A simple and sensitive fluorescence assay for monoamine oxidase and diamine oxidase. J Pharmacol Exp Ther 1968;163:386-92.

Wurtman RJ, Axelrod J. A sensitive and specific assay for the estimation of monoamine oxidase. Biochem Pharm 1963;12:1439-40.

Sweetman AJ, Weetman DF. Polarographic assay of monoamine oxidase. Br J Pharmacol 1969;37:550.

Weissbach H, Smith TE, Daly JW, Witkop B, Udenfriend SA. Rapid spectrophotometric assay of monoamine oxidase based on the rate of disappearance of kynuramine. J Biol Chem 1960:235:1160-3.

Robert F, Cerza MD. Beta-selective monoamine oxidase inhibitors and cardiac anesthesia. J Cardiothorac Vasc Anesth 1995;9:717-9.

Yu ZF, Kong LD, Chen Y. Antidepressant activity of aqueous extracts of Curcuma longa in mice. J Ethnopharmacol 2002;83:161-5.

Robinson DS. Monoamine oxidase inhibitors: a new generation. Psychopharmacol Bull 2002;36:124–38.

Published

01-02-2015

How to Cite

Mute, V. M., and S. L. Bodhankar. “ANTIDEPRESSANT LIKE EFFECT OF NEWLY SYNTHESIZED COMPOUND 2[(N- BENZYLACETAMIDO) MERCAPTO] BENZIMIDAZOLE (VS 25) AND ITS POSSIBLE MECHANISM BY INHIBITION OF MONOAMINE OXIDASE ENZYME IN MICE”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 2, Feb. 2015, pp. 407-10, https://journals.innovareacademics.in/index.php/ijpps/article/view/4066.

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