Effect of gabaergic, glutamatergic, antipsychotic and antidepressant drugs on pilocarpine-induced seizures and status epilepticus.
This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Fluoxetine (10 and 20 mg/kg), NMDA (N-methyl-D-aspartate, 10 and 20 mg/kg), amitriptyline (25 and 50 mg/kg), ketamine (0.5 and 1.0 mg/kg), gabapentin (100 and 150 mg/kg) and pimozide (10 and 20 mg/kg) were administered intraperitoneally, 30 min prior to pilocarpine (400mg/kg, s.c.). The animals were observed (24h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. Fluoxetine, amitriptyline, NMDA, and pimozide had proconvulsant effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures and/or mortality. Gabapentin and ketamine protected against seizures and reduced the latency to first seizure. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with epilepsy because of the possibility of potentiating convulsive process toxicity.
Freitas
R M
RM
Department of Physiology and Pharmacology, Laboratory of Neuropharmacology, School of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1127, Fortaleza 60431-970, CE, Brazil. rivmendes@bol.com.br
Sousa
F C F
FC
Viana
G S B
GS
Fonteles
M M F
MM
D000588:Amines / Q000627:therapeutic use; D000639:Amitriptyline / Q000627:therapeutic use; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005473:Fluoxetine / Q000627:therapeutic use; D000077206:Gabapentin; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D016202:N-Methylaspartate / Q000627:therapeutic use; D010862:Pilocarpine / Q000494:pharmacology*; D010868:Pimozide / Q000627:therapeutic use; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy* / Q000401:mortality; D013226:Status Epilepticus / Q000139:chemically induced* / Q000188:drug therapy* / Q000401:mortality; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
D000588:Amines; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018721:Muscarinic Agonists; D005473:Fluoxetine; D010862:Pilocarpine; D000639:Amitriptyline; D010868:Pimozide; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D007649:Ketamine; D000077206:Gabapentin