J Pharm Pharmacogn Res 2(Suppl. 1): S67, 2014
Special supplement with the abstract book of LATINFARMA 2013
C 023: PRECLINICAL STUDIES OF A NEW HYBRID MOLECULE WITH NEUROPROTECTIVE EFFECTS IN THE TREATMENT OF CEREBRAL ISCHEMIA
Nuñez Y1, Pardo G2, Ramírez J1, García L1, Delgado R1, Merino N1, Valdés O1, Ochoa E2, Verdecia Y2, Iglesias L1, Onofre D3, Salbego C3, Hansel G3, Nicoloso E3, Porto M1.
Introduction: Cerebral ischemia has a high incidence at present, their frequency increases with increasing life expectancy and the drugs available have low effectiveness. Clinical evidence has shown therapeutic failure of neuroprotective drugs, often caused by the use of drugs that act on a single mediator of damage in a disease that involves a complex variety of events. That is why the study of multiligands compounds that may affect several steps of the ischemic cascade, could be an attractive therapeutic option for this disease.
Material and methods: In the present work we evaluated, a novel 1,5benzodiazepines with the presence of a 1,4 dihydropyridine moiety fused to the benzodiazepine ring (JM-20) in different experimental models associated with ischemic brain damage, including behavioral models to evaluate GABAergic activity, cellular models for evaluate cytotoxicity induced by glutamate, hydrogen peroxide and oxygen glucose deprivation. Also we evaluated the effect of JM-20 on different parameters associated with mitochondrial dysfunction and on histological, behavioral and biochemical alterations in animal models of stroke.
Results: The main results obtained show that JM-20 has a neurosedative profile similar to diazepam, however the presence of the dihydropyridine moiety in their structure, could be inhibiting damage associated exacerbated calcium in flux. Moreover, JM-20 showed strong neuroprotective effect in animals and cell models associated with the cerebral ischemia and on different parameters of mitocondrial dysfunction responsible of the neuronal death.