Antipsychotic drugs inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes

Haloperidol (HAL), olanzapine (OLZ), and sulpiride (SULP) are antipsychotic drugs widely used in the pharmacotherapy of psychopathological symptoms observed in schizophrenia or mood-related psychotic symptoms in affective disorders. Here, we tested the in vitro effects of different concentrations of a typical (HAL) and two atypical (OLZ and SULP) antipsychotic drugs on ectonucleotidase activities from zebrafish brain membranes. HAL inhibited ATP (28.9%) and ADP (26.5%) hydrolysis only at 250 microM. OLZ decreased ATPase activity at all concentrations tested (23.8-60.7%). SULP did not promote significant changes on ATP hydrolysis but inhibited ADP hydrolysis at 250 microM (25.6%). All drugs tested, HAL, OLZ, and SULP, did not promote any significant changes on 5'-nucleotidase activity in the brain membranes of zebrafish. These findings demonstrated that antipsychotic drugs could inhibit NTPDase activities whereas did not change 5'-nucleotidase. Such modulation can alter the adenosine levels, since the ectonucleotidase pathway is an important source of extracellular adenosine. Thus, it is possible to suggest that changes promoted by antipsychotic drugs in the bilayer membrane could alter the NTPDase activities, modulating extracellular ATP and adenosine levels.