RESUMO
Injection of large doses of ammonia (1.2g/kg, i.p.) was used to induce acute toxicity in mice which was characterized by hyperresponsiveness, taquipnea, clonic and tonic seizures and death. Pretreatment with 20, 40, or 80 mg/Kg, i.p., of ketamine increased 30 to 55% survival rate. This pretreatment significantly retarded the beginning of the first tonic convulsion attenuating its intensity and delayed the time of the animal death; but did not alter the onset of the first clonic seizures. These experiments may be an evidence that support the hypothesis that seizures due to hyperammonemia involve activation of excitatory amino acid receptors.
Assuntos
Amônia/intoxicação , Ketamina/uso terapêutico , Animais , Masculino , Camundongos , Intoxicação/tratamento farmacológicoRESUMO
Spinal seizures evoked by sudden cooling (SSSC) were used to investigate the anticonvulsant activity of ketamine (KET) injected either intralymphatically (i.l., 5-40 mg/kg) or intrathecally (i.t., 0.5-1.0 mumol/20 microliters) using isolated spinal cord-hindleg preparation. KET inhibited the tonic phase and prolonged the clonic phase in a dose-dependent manner. The cionic phase was depressed or totally blocked at KET doses of 80-160 mg/kg, i.l. or 2 mumol/20 microliters, i.t. This depression was not prevented by i.t. administration of concanavalin A. The latency of onset of seizures was also increased by KET. KET abolishes the tonic-extensor phase of SSSC in which activation of N-methyl-D-aspartate-receptors may play a role.
Assuntos
Temperatura Baixa , Epilepsia/tratamento farmacológico , Ketamina/farmacologia , Medula Espinal/efeitos dos fármacos , Animais , Bufo marinus , Epilepsia/etiologia , Técnicas In Vitro , Fatores de TempoRESUMO
The effect of low doses of urethane on three phases of spinal seizures evoked by sudden cooling (SSSC) of toad isolated spinal cord was studied. In control toads, SSSC began with a latency of 91 +/- 3 sec (mean +/- S.E.M.) exhibiting brief tremors, followed by clonic muscle contractions and finally reaching a tonic contraction (tonic phase). The latency of onset of seizures was significantly enhanced. The tonic phase was markedly abolished in toads pretreated intralymphatically with 0.15 g/kg of urethane. Tremors were the only phase observed in 55% of toads that received doses of 0.2 g/kg, and a total blockade of seizures was seen after doses of 0.25 g/kg of urethane in 50% of the preparations. A possible depressant effect of urethane on transmission mediated by excitatory amino acids is suggested.