Interaction mechanisms of imipramine and desipramine with enkephalin-degrading aminopeptidases in vitro |
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| Affiliation: | 1. Department of Human Genetics, College of Biomedical Sciences, Technology & Research, Sri Ramachandra University, Porur, Chennai- 600 116, India;2. Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai- 600 025, India;3. Department of Bioinformatics, Alagappa University, Karaikudi- 630003, India;4. Department of Biotechnology, Indian Institute of Technology, Madras (IIT M), Chennai- 600 025, India;5. Department of Medicinal Chemistry, College of Biomedical Sciences, Technology & Research,Sri Ramachandra University, Porur, Chennai- 600 116, India;6. Department of Conservative Dentistry and Endodontics, College of Dental Sciences, Sri Ramachandra University, Porur, Chennai-600 116, India;7. Department of Community Medicine, Sri Ramachandra Medical College & Research Institute, Sri Ramachandra University, Porur, Chennai-600 116, India;1. Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India;2. Department of Medicinal Chemistry, NIPER-HYD, Hyderabad, India;3. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India |
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| Abstract: | In the last few years, considerable evidence has appeared concerning the importance of the opioid systems in the action mechanism of some antidepressant drugs. This action mechanism could be mediated through the inhibition of the enzymes reponsible for enkephalin degradation. In this sense, imipramine treatment in vivo increases the enkephalin levels, and this effect is enhanced by inhibitors of enkephalin-degrading enzymes. The present work shows the effects in vitro of imipramine and its active metabolite desipramine on the activities of two membrane-bound enkephalin-degrading aminopeptidases present in rat brain. Imipramine and desipramine in vitro do not affect the aminopeptidase M activity, but they reversibly inhibits the aminoeptidase MII. The enzyme kinetic analysis shows that this enzyme molecule has two different binding sites for each drug, which exert a mixed type enzyme inhibition. |
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