Interaction of Antipsychotic Drugs with Sucrase, Kinetics and Structural Study

Title:Interaction of Antipsychotic Drugs with Sucrase, Kinetics and Structural Study

Volume: 12 Issue: 1

Author(s): Narges Jafari, Helia Dehganpour, Nava Ghavanini, Hamidreza Mollasalehi and Dariush Minai-Tehrani*

Affiliation:

• BioResearch Lab, Faculty of Biological Sciences & Technology, Shahid Beheshti University, G.C. Tehran,Iran

Keywords: Enzyme, drug, inhibition, kinetics, conformational changes, schizophrenia.

Abstract: Background: In patients with the Congenital Sucrase-Isomaltase Deficiency (CSID), who lack intestinal sucrase-isomaltase enzyme, a suspension of yeast sucrase is applied as a drug to compensate the enzyme deficiency. While antipsychotic drugs are used for the treatment of schizophrenia, administering multiple drugs at the same time may counteract each other.

Methods: In this study, the interaction between trifluoperazine and haloperidol as antipsychotic drugs on oral drug yeast sucrase was investigated. In this regard, the kinetic parameters of enzyme were determined in the presence or absence of the drugs. The kinetic parameters of the drugs such as Ki and IC50 were also calculated. Lineweaver - Burk plot was used to reveal the type of inhibition.

Results: The results showed that both drugs could reduce sucrase activity and decrease the Vmax of the enzyme by non-competitive inhibition. The IC50 and Ki values of the drugs were determined to be 0.7 and 0.068 mM and 0.45 and 0.063 mM for haloperidol and trifluoperazine, respectively. The results suggested that trifluoperazine binds to the enzyme with higher affinity than haloperidol. Fluorescence measurement was used for conformational investigations of the drugs and sucrase interaction. It was shown that the drugs bind to free enzyme and enzyme-substrate complex which are accompanied with hyperchromicity. This suggests that tryptophan residues of the enzyme transferred to hydrophobic medium after binding of the drugs to the enzyme.

Conclusion: The finding of this research revealed that both trifluoperazine and haloperidol could inhibit sucrase in non-competitive manner. The kinetic parameters and conformational changes due to binding of trifluoperazine to the enzyme were different from that of haloperidol.

Cite this article as:

Jafari Narges, Dehganpour Helia, Ghavanini Nava, Mollasalehi Hamidreza and Minai-Tehrani Dariush*, Interaction of Antipsychotic Drugs with Sucrase, Kinetics and Structural Study, Current Clinical Pharmacology 2017; 12 (1) . https://dx.doi.org/10.2174/1574884712666170118145901

DOI https://dx.doi.org/10.2174/1574884712666170118145901	Print ISSN 1574-8847
Publisher Name Bentham Science Publisher	Online ISSN 2212-3938