Antidepressant drugs in convulsive seizures: Pre-clinical evaluation of duloxetine in mice.
Convulsive seizures (CS) are deleterious consequences of acute cerebral insults and prejudicial events in epilepsy, affecting more than 50 million people worldwide. Molecular mechanisms of depression and epilepsy include an imbalance between excitatory and inhibitory neurotransmission provoking oxidative stress (OS). OS is intimately linked to the origin and evolution of CS and is modulated by antidepressant and anticonvulsant drugs. Although newer antidepressants have exhibited a possible protective role in CS, studies analyzing serotonin and norepinephrine reuptake inhibitors merit to be further investigated. Thus, this study challenged the traditional model of pentylenetetrazol-induced CS, with only one administration of duloxetine. Male Swiss mice were treated with duloxetine (dose corresponding to the therapeutic range for human depression or greater, by allometric calculation; 10, 20 or 40 mg/kg), 30 min before pentylenetetrazol. Behavioral and electroencephalographic alterations were monitored. Lipid peroxidation, nitrites and catalase and superoxidase activities were measured in cortex. Behavioral and electroencephalographic results suggested a possible biphasic effect of duloxetine on CS, with anticonvulsant actions at therapeutic doses and a proconvulsant effect at higher doses. Duloxetine (20 mg/kg) also prevented lipid peroxidation and decreased catalase and superoxide dismutase activities in the cerebral cortex, with no influence on nitrites levels. These data demonstrated an anticonvulsant effect of duloxetine in CS for the first time. This extra anticonvulsant effect may allow the doses of anticonvulsants to be reduced, causing fewer side effects and possibly decreasing morbidity and mortality due to drug interactions in polytherapy.
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Belém, Brazil.
Danielle
D
Santana-Coelho
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Belém, Brazil.
José Rogerio
JR
Souza-Monteiro
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Belém, Brazil.
Ricardo S O
RSO
Paraense
Laboratório de Bioquímica do Exercício, Centro de Educação Física e Desportos (CEFD), Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
Guilherme L
GL
Busanello
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Belém, Brazil.
Gabriela P F
GPF
Arrifano
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Belém, Brazil.
Jackson R
JR
Mendonça
Laboratório de Bioquímica do Exercício, Centro de Educação Física e Desportos (CEFD), Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
Mauro E P
MEP
Silveira-Junior
Laboratório de Bioquímica do Exercício, Centro de Educação Física e Desportos (CEFD), Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil.
Luiz Fernando F
LFF
Royes
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Belém, Brazil. Electronic address: maria.elena.crespo.lopez@gmail.com.
Maria Elena
ME
Crespo-López
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism*
D000927:Anticonvulsants; D000928:Antidepressive Agents; D000068736:Duloxetine Hydrochloride
Anticonvulsant; Antidepressant; Duloxetine; Oxidative stress; SNRI; Seizures