Potential Central Nervous System effects of the synthetic flavonoid 3,3-dibromoflavanone.

J. HIGGS; C. WASOWSKI; M. MARDER

Córdoba, Argentina

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigacion en Neurociencias; 2012

Sociedad Argentina de Investigación en Neurociencias

The pharmacotherapy for mental disorders and the treatment of pain is an active area of investigation. We have demonstrated the significance of flavonoids on the central nervous system (CNS) and classified them in: 1) natural or synthetic substituted flavones with affinity for the benzodiazepine binding site of the GABAA receptor with anxiolytic action; 2) glycosilated flavonoids with sedative, hypnotic and antinociceptive properties in vivo presumably acting via an opioid mechanism of action. From our library of natural and synthetic flavonoid derivatives, 3,3-dibromoflavanone (DBF) evidenced affinity for the m-opioid receptor. We have synthesized and studied its effects on the CNS. DBF showed no sedative, anxiolytic, antidepressant or motor incoordination effects. It showed antinociceptive activity in which adrenoceptors, 5-HT2, ä and ê opioid receptors are not involved. Naltrexone, a nonselective opioid receptors antagonist, totally blocked DBF antinociception. DBF inhibited the specific binding of [3H]DAMGO (Ki: 0.85 ± 0.26 ìM) in mice cerebral membranes. These results will contribute to develop new drugs with CNS effects from flavanone structures.