New antipsychotic agents? Investigation of sinergic interaction between clozapine, doxicicline and/or canabidiol

• Grant number: 18/20407-1
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2019
• Effective date (End): December 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal researcher: Elaine Aparecida Del Bel Belluz Guimarães
• Grantee: Anna Beatriz Saito van Oosten
• Home Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/25029-4 - Contribution of the neuroinflamation to L-DOPA induced dyskinesia, AP.TEM

Abstract

Schizophrenia is a chronic mental disorder with multiple symptoms, classified in positive, negative or cognitive. The antipsychotics are the main treatment for schizophrenia symptoms; however, they are not effective for all patients. Furthermore, antipsychotics use has wide range of side effects, which decrease the patient's adherence to the treatment. Therefore, the pursuit for new pharmacological strategies to treat schizophrenic symptoms is theme of extensive research. The preclinical trials represent an opportunity to expand the knowledge about the pharmacological profile of new drugs. Recently, the reconceptualization about a drug already clinically used for another designation is an interesting strategy. The goal of this work is investigate the potential synergic interaction between the antipsychotic clozapine and experimental compounds with antipsychotic-like actions: (I) which modulate the endocannabinoid system (canabidiol) and (II) the neuroinflammation process (doxicicline). The synergic relationship between low doses of these drugs exhibit potential for the increase of therapeutic efficacy with decreased side effects. Predictive animal models for antipsychotic-like action (impairment in pre-pulse inhibition test, in object recognition and hyperlocomotion induced for either amphetamine or MK801) will be used with complementary molecular analysis (immunohistochemistry and zymography).