Journal of Pharmacy & Pharmacognosy Research (JPPRes) | Journal of Pharmacy & Pharmacognosy Research

J Pharm Pharmacogn Res 2(Suppl. 1): S67, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

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.

¹Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba, E-mail: yaniernf@infomed.sld.cu

²Centro de Estudio para las Investigaciones y Evaluaciones Biológicas, Instituto de Farmacia y Alimentos, Universidad de La Habana, ave. 23 # 21425 e/214 y 222, La Coronela, La Lisa, CP 13600, La Habana, Cuba.

³Laboratorio de Síntesis Orgánica de La Facultad de Química de La Universidad de La Habana (Zapata s/n entre G y Carlitos Aguirre, Vedado Plaza de la Revolución, CP 10400, La Habana, Cuba.

⁴Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo, Porto Alegre, RS 90035-003, Brazil.

Abstract

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.