Neuronal death pathway induced by methylecgonidine, cocaine pyrolysis product, and its involvement in addiction

• Grant number: 11/02734-6
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2011 - July 31, 2013
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Tania Marcourakis
• Grantee: Tania Marcourakis
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Crack cocaine use has increased in the last years when compared to other routes of cocaine administration. Its quicker and stronger effects are advantageous as well as its easier use without the need of needles. Smoking crack cocaine involves inhaling not only cocaine, but also its pyrolysis product, methylecgonidine (AEME). There are evidences showing the neurotoxicity of cocaine, but little is known about AEME neurotoxicity and its involvement in addiction. Studies in vitro performed previously in our group showed AEME can be more neurotoxic than cocaine, once lower concentrations lead to neuronal death. In this same study, our results showed that, in equipotent concentrations, the concomitant incubation of both compounds during 48 hours had an additive neurotoxic effect. As smoking crack cocaine abusers are exposed to both cocaine and AEME, our results suggest a higher susceptibility to neurotoxicity in smoking crack cocaine than with cocaine itself. This project is an extension of the previous work, where the master degree project will investigate the mechanisms involved in neuronal death, with more interest in apoptose and necrose signaling, while the PhD project will investigate AEME participation in addiction. Our intention is to elucidate if this substance, together with cocaine, is involved in the great devastating potential of crack cocaine. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TAMBORELLI GARCIA, RAPHAEL CAIO; TORRES, LARISSA LOBO; MUNHOZ DATI, LIVIA MENDONCA; DE MELO LOUREIRO, ANA PAULA; AFECHE, SOLANGE CASTRO; LOPES SANDOVAL, MARIA REGINA; MARCOURAKIS, TANIA. Anhydroecgonine methyl ester (AEME), a cocaine pyrolysis product, impairs glutathione-related enzymes response and increases lipid peroxidation in the hippocampal cell culture. TOXICOLOGY REPORTS, v. 6, p. 1223-1229, 2019. (11/02734-6, 09/11149-0)

TAMBORELLI GARCIA, RAPHAEL CAIO; TORRES, LARISSA HELENA; BALESTRIN, NATALIA TRIGO; ANDRIOLI, TATIANA COSTA; FLORIO, JORGE CAMILO; RODRIGUES DE OLIVEIRA, CAROLINA DIZIOLI; DA COSTA, JOSE LUIZ; YONAMINE, MAURICIO; LOPES SANDOVAL, MARIA REGINA; CAMARINI, ROSANA; et al. Anhydroecgonine methyl ester, a cocaine pyrolysis product, may contribute to cocaine behavioral sensitization. Toxicology, v. 376, n. SI, p. 44-50, FEB 1 2017. (11/02734-6)

TAMBORELLI GARCIA, RAPHAEL CAIO; MUNHOZ DATI, LIVIA MENDONA; FUKUDA, SUELEN; LOBO TORRES, LARISSA HELENA; MOURA, SIDNEI; DE CARVALHO, NATHALIA DELAZERI; CARRETTIERO, DANIEL CARNEIRO; CAMARINI, ROSANA; LEVADA-PIRES, ADRIANA CRISTINA; YONAMINE, MAURICIO; et al. Neurotoxicity of Anhydroecgonine Methyl Ester, a Crack Cocaine Pyrolysis Product. TOXICOLOGICAL SCIENCES, v. 128, n. 1, p. 223-234, JUL 2012. (11/02734-6, 09/11149-0)

TAMBORELLI GARCIA, RAPHAEL CAIO; MUNHOZ DATI, LIVIA MENDONCA; TORRES, LARISSA HELENA; ALENCAR DA SILVA, MARIANA AGUILERA; BERTO UDO, MARIANA SAYURI; FRANCIS ABDALLA, FERNANDO MAURICIO; DA COSTA, JOSE LUIZ; GORJAO, RENATA; AFECHE, SOLANGE CASTRO; YONAMINE, MAURICIO; et al. M-1 and M-3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product. SCIENTIFIC REPORTS, v. 5, DEC 2 2015. (11/02734-6, 09/11149-0)