THE INVESTIGATION OF THE INTERACTION OF SEVERAL ANTIPSYCHOTIC DRUGS WITH HUMAN CHOLINESTERASE ENZYMES

THE INVESTIGATION OF THE INTERACTION OF SEVERAL ANTIPSYCHOTIC DRUGS WITH HUMAN CHOLINESTERASE ENZYMES

Phenothiazines and butyrophenones are one of the important antipsychotic group of drugs. They have been utilized for many years for treatment of schizophrenia and other psychotic disorders. They are the main constituents of the first generation, also referred as typical, antipsychotic drugs. They are known for their potential to antagonize dopamine D2 receptors. With respect to their structures, they are able to cross the blood brain barrier and interact with various types of receptors. In order to investigate their potential to interact with cholinesterase enzymes, within this research, we have designed a series of experiments. Although, earlier studies have shown that some of those compounds have the potential to inhibit cholinesterase enzyme, for the first time, we have evaluated their potential to inhibit human isoforms of acetylcholinesterase and butyrylcholinesterase. The results strongly pointed out that phenothiazines are selective and potent inhibitors of the human butyrylcholinesterase enzyme.

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  • Cummings, J. L. (2000). Cholinesterase inhibitors: A new class of psychotropic compounds. Am J Pscyhiat, 157(January), 4–15.
  • Darvesh, S., Macdonald, I. R., & Martin, E. (2013). Selectivity of phenothiazine cholinesterase inhibitors for neurotransmitter systems. Bioorg Med Chem LettT, 23(13), 3822–3825.
  • Darvesh, S., McDonald, R. S., Penwell, A., Conrad, S., Darvesh, K. V., Mataija, D., … Martin, E. (2005). Structure-activity relationships for inhibition of human cholinesterases by alkyl amide phenothiazine derivatives. Bioorg Med Chem, 13(1), 211–222.
  • Darvesh, S., Pottie, I. R., Darvesh, K. V., McDonald, R. S., Walsh, R., Conrad, S., … Martin, E. (2010). Differential binding of phenothiazine urea derivatives to wild-type human cholinesterases and butyrylcholinesterase mutants. Bioorg Med Chem, 18(6), 2232–2244.
  • Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol, 7(2), 88–95.
  • Ercetin, T., Senol, F. S., Erdogan Orhan, I., & Toker, G. (2012). Comparative assessment of antioxidant and cholinesterase inhibitory properties of the marigold extracts from Calendula arvensis L. and Calendula officinalis L. Ind Crop Prod, 36(1), 203–208.
  • Extoxnet. (1993). Cholinesterase Inhibition. Retrieved December 1, 2016, from http://pmep.cce.cornell.edu/profiles/extoxnet/TIB/cholinesterase.html
  • Gulcan, H. O., Unlu, S., Esiringu, İ., Ercetin, T., Sahin, Y., Oz, D., & Sahin, M. F. (2014). Design, synthesis and biological evaluation of novel 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydrobenzo[c]chromen-6-one derivatives as potential cholinesterase inhibitors. Bioorg Med Chem, 22(19), 5141–5154.
  • Jaszczyszyn, A., Ga̧siorowski, K., Świa̧tek, P., Malinka, W., Cieślik-Boczula, K., Petrus, J., & CzarnikMatusewicz, B. (2012). Chemical structure of phenothiazines and their biological activity. Pharmacol Rep, 64(1), 16–23.
  • Mayoclinic. (2016). Phenothiazine (Oral Route, Parenteral Route, Rectal Route) Description and Brand Names - Mayo Clinic. Retrieved November 1, 2016, from http://www.mayoclinic.org/drugssupplements/phenothiazine-oral-route-parenteral-route-rectal-route/description/drg-20070394
  • Nasello, A. G., Gidali, D., & Felicio, L. F. (2003). A comparative study of the anticholinesterase activity of several antipsychotic agents. Pharmacol Biochem Be, 75(4), 895–901.
  • Pope, C., Karanth, S., & Liu, J. (2005). Pharmacology and toxicology of cholinesterase inhibitors: Uses and misuses of a common mechanism of action. Environ Toxicol Phar, 19(3), 433–446.
  • Rahman, A., & Choudhary, M. I. (2014). Drug Design and Discovery in Alzheimer’s Disease. Drug Design and Discovery in Alzheimer’s Disease. https://doi.org/10.1016/B978-0-12-803959-5.50018-0 Sims, J. (1995). The extrapyramidal effects of phenothiazines on patients. NURS TIMES. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7501500
  • Sudeshna, G., & Parimal, K. (2010). Multiple non-psychiatric effects of phenothiazines: A review.Eue J Pharmacol, 648(1–3), 6–14.