Effect of anxiolytic, antidepressant, and antipsychotic drugs on cocaine-induced seizures and mortality.
Cocaine abuse may lead to overdose (related to seizures and/or status epilepticus) and to diseases (schizophrenia, depression, and anxiety). This work was designed to study the influence of drugs used to treat psychopathologies associated with cocaine abuse on cocaine-induced seizures and mortality in mice. Fluoxetine (10, 20, 40 mg/kg), imipramine and buspirone (5, 10 mg/kg), pimozide (10, 20 mg/kg), lithium (56.3, 112.5 mg/kg), and naltrexone (25, 50 mg/kg) were administered intraperitoneally, 30 minutes prior to cocaine (90 mg/kg, ip). The animals were observed (30 minutes) to determine: latency to first seizure, number of seizures, and number of deaths after cocaine overdose. Fluoxetine, imipramine, buspirone, and pimozide had pro- or anticonvulsant effects depending on the dose. Smaller doses protected and higher doses increased cocaine-induced seizures and/or mortality. Naltrexone worsened and lithium protected against seizures. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with cocaine addiction because of the possibility of potentiating cocaine toxicity.
Macêdo
Danielle Silveira
DS
Department of Physiology and Pharmacology, Federal University of Ceará, Ceará, Brazil.
Santos
Rachel S
RS
Belchior
Luciana D
LD
Neto
Manoel Andrade
MA
Vasconcelos
Silvânia Maria Mendes
SM
Lima
Vera Targino Moreira
VT
Fonteles
Marta Maria França
MM
Viana
Glauce Socorro Barros
GS
de Sousa
Francisca Cléa Florenço
FC
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003042:Cocaine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003042:Cocaine