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ANTIOXIDANT ACTIVITY OF SELECTED ATYPICAL ANTIPSYCHOTICS


                                                   Konstantin Kostić

                                Center for talented youth Belgrade II, Belgrade, kostic.prof@gmail.com
                           Supervisor: dr Milan Nikolić, Faculty of Chemistry,  University of Belgrade


          INTRODUCTION


          Atypical  antipsychotics  are  the  drugs  of  choice  in  the
          treatment  of  schizophrenia.  They  are  antagonists  of  the
          dopamine and serotonin receptors in the brain.
          It  is  believed  that  oxidative  stress  (an  imbalance  between
          formation and removal of reactive oxygen species) plays an
          important role in the etiology of psychosis, as well as many
          other    chronic     conditions    (atherosclerosis,
          neurodegenerative  diseases,  diabetes,  etc.).  Therefore,  the
          antioxidant activity of drugs may contribute to their clinical
          efficacy, as part of their pleiotropic (unexpected) effects.

          OBJECTIVE
          The  aim  of  this  work  was  to  investigate  the  antioxidant
          activities of selected atypical antipsychotics, using standard   Figure  1:  Antioxidant  activity  of  selected  atypical
          in vitro spectrophotometric assays.                  antipsychotics

          MATERIALS AND METHODS                                As  expected,  ascorbic  acid  and  Trolox  have  showed  a
                                                               marked  antioxidant  activity  (***)  in  all  essays.  From  the
          In this study, the antioxidant activity of the top five most-  study drugs, Clozapine showed significant reduction ability
          used atypical antipsychotics: Clozapine (Clo), Aripriprazole   (**)  toward  redox-active  metals  and  the  detoxification  of
          (Ari), Quetiapine (Que), Risperidone (Ris) and Olanzapine   free  radicals.  Aripiprazole  and  Risperidone  did  not  show
          (Ola) was evaluated.                                 any  antioxidant  properties,  while  Quetiapine  and  (a  little
                                                               more)  Olanzapine  had  a  mild  (*)  radical  scavenging
          The  active  substances  of  commercial  drug  preparations
          were  isolated  by  methanol  extraction.  Trolox®  (water   activity.
          soluble analog of vitamin E) and vitamin C (ascorbic acid)
          were  used  as  standard  probes.  The  concentration  of  the   CONCLUSION
          tested compounds was 1 mg/mL.
            - TEST OF TOTAL REDUCING POWER                     Atypical  antidepressants  showed  significantly  different
                                             3+
          This assay is  based on the reduction of Fe /  ferricyanide   antioxidant properties,  which  may influence the choice of
                     2+
          complex to Fe  form, with the formation of Prussian blue.   drug  from  this  group  for  therapeutic  purposes.  Research
                                                               should  be  extended,  by  examining  possible  antioxidant
            - TOTAL ANTIOXIDANT CAPACITY                       activity  of  these  drugs  to  physiologically  important  free
                                                               radicals (e.g. superoxide anion and hydroxyl radical).
          In this test the antioxidant reduces the Mo(VI) to Mo(V),
          with the formation of the green phospho/Mo(V) complex.
                                                               LITERATURE
            - DPPH AND ABTS TEST
          Removal of free radicals by the analyzed substances was   [1]  Stahl's  Essential  Psychopharmacology:  Neuroscientific
          estimated  following  the  decolorization  of  purple  DPPH•   Basis  and  Practical  Applications,  3rd  edition,  Cambridge
                                                         +
          (2,2-diphenyl-1-picrylhydrazyl) and a dark green ABTS•    University Press (2008)
          (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)).
                                                               [2]  Alam MN, Bristi NJ, Rafiquzzaman M. Review on in
                                                               vivo and in vitro methods evaluation of antioxidant activity.
          RESULTS                                              Saudi Pharm J. 2013; 21(2):143-52.

          The  results  are  presented  graphically  (Figure  1),  as  the
          mean  of  two  independent  experiments  performed  in
          duplicate.
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