RESUMO
Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord. We show that acute glycinergic blockade with strychnine or GABAergic blockade with bicuculline had no significant effects on motor activity and on motor neuron survival. However, chronic bicuculline infusion, but not strychnine, induced ipsilateral gait alterations, phalange flaccidity and significant motor neuron loss, and these effects were prevented by AMPA receptor blockade with CNQX but not by NMDA receptor blockade with MK801. In addition, we demonstrate that the chronic infusion of bicuculline enhanced the excitotoxic effect of AMPA, causing faster bilateral paralysis and increasing motor neuron loss. These findings indicate a relevant role of GABAergic inhibitory circuits in the regulation of motor neuron excitability and suggest that their alterations may be involved in the neurodegeneration processes characteristic of motor neuron diseases such as amyotrophic lateral sclerosis.
Assuntos
Bicuculina/toxicidade , Antagonistas GABAérgicos/toxicidade , Atividade Motora/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Degeneração Neural/induzido quimicamente , Medula Espinal/efeitos dos fármacos , Estricnina/toxicidade , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Atrofia/induzido quimicamente , Bicuculina/antagonistas & inibidores , Maleato de Dizocilpina/farmacologia , Interações Medicamentosas , Marcha/efeitos dos fármacos , Masculino , Hipotonia Muscular/induzido quimicamente , Ratos , Receptores de Glicina/antagonistas & inibidores , Estricnina/antagonistas & inibidores , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/toxicidadeRESUMO
Cymbopogon winterianus (Poaceae) is used for its analgesic, anxiolytic and anticonvulsant properties in Brazilian folk medicine. This report aimed to perform phythochemical screening and to investigate the possible anticonvulsant effects of the essential oil (EO) from fresh leaves of C. winterianus in different models of epilepsy. The phytochemical analysis of EO showed presence of geraniol (40.06%), citronellal (27.44%) and citronellol (10.45%) as the main compounds. A behavioral screening demonstrated that EO (100, 200 and 400mg/kg; ip) caused depressant activity on CNS. When administered concurrently, EO (200 and 400mg/kg, ip) significantly reduced the number of animals that exhibited PTZ- and PIC-induced seizures in 50% of the experimental animals (p<0.05). Additionally, EO (100, 200 and 400mg/kg, ip) significantly increased (p<0.05) the latencies of clonic seizures induced by STR. Our results demonstrated a possible activity anticonvulsant of the EO.
Assuntos
Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Folhas de Planta/química , Poaceae/química , Animais , Comportamento Animal/efeitos dos fármacos , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Pentilenotetrazol/toxicidade , Fenitoína/farmacologia , Fitoterapia , Picrotoxina/toxicidade , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Estricnina/toxicidadeRESUMO
A reinvestigation of Strychnos guianensis resulted in the isolation of a colored quaternary bisindole alkaloid from the stem bark. The structure of this new substance, guiaflavine (1), was defined by detailed spectroscopic methods and comparison with model compounds.
Assuntos
Indóis , Quinolizinas/isolamento & purificação , Estricnina/análogos & derivados , Árvores , Animais , Cromatografia em Camada Fina , Masculino , Camundongos , Extratos Vegetais/química , Quinolizinas/toxicidade , América do Sul , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Estricnina/isolamento & purificação , Estricnina/toxicidadeRESUMO
Baccharis serraefolia is a widely used plant to treat diarrhoea in Mexican traditional medicine. Although the methanolic extract of this plant has shown an important dose-dependent spasmolytic activity, its underlying mechanism has not been studied. In the present work, the methanolic extract of B. serraefolia significantly delayed the onset of tonic seizures induced by strychnine and pentylenetetrazol; besides, it diminished the death rate and number of animals that exhibited convulsions. It produced potentiation of the hypnotic effect of pentobarbital. Oral administration produced an inhibition of gastrointestinal transit in mice as effective as that produced by loperamide. As to the effect on smooth muscles, the active extract produced an inhibition of contraction induced electrically, which could not be reversed by naloxone. The calcium concentration-contraction curve showed a rightward displacement when the extract was added to isolated guinea pig ileum depolarized with high K+ and cumulative concentrations of Ca2+. The results suggest that the methanolic extract does not interact with classical opiate receptors and its effects, at least that produced on smooth muscle, may be due to a probable interference with calcium influx and/or calcium release from an intra-cellular store.
Assuntos
Antidiarreicos/farmacologia , Cálcio/antagonistas & inibidores , Músculo Liso/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Convulsões/prevenção & controle , Administração Oral , Análise de Variância , Animais , Convulsivantes/administração & dosagem , Convulsivantes/toxicidade , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Estimulação Elétrica , Trânsito Gastrointestinal/efeitos dos fármacos , Cobaias , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Íleo/efeitos dos fármacos , Íleo/metabolismo , Loperamida/farmacologia , Masculino , Medicina Tradicional , Metanol/química , México , Camundongos , Camundongos Endogâmicos BALB C , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Pentobarbital/administração & dosagem , Pentobarbital/farmacologia , Pentilenotetrazol/administração & dosagem , Pentilenotetrazol/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Plantas Medicinais , Convulsões/tratamento farmacológico , Convulsões/mortalidade , Estricnina/administração & dosagem , Estricnina/toxicidadeRESUMO
Catnip or catmint (Nepeta cataria) is a plant used extensively to treat human diseases and in toys for pets. We investigated the effects of acute and long-term administration of the plant on some behaviors of mice. The plant was fed as 10% of the normal diet for 2 h/d for 1 or 7 d. Acute and long-term dosing increased both rearing and locomotion frequencies observed in an open field. Acute exposure to catnip increased stereotyped behavior and susceptibility to seizures, did not interfere with haloperidol-induced catalepsy, and decreased sleeping time after sodium pentobarbital administration. Long-term exposure induced tolerance to stereotypic behavior, catalepsy and sleeping time, and increased the susceptibility to seizures induced by picrotoxin and strychnine. An amphetamine-like effect of catnip was suggested to explain the acute effects, while dispositional and functional adaptative changes were considered involved with the long-term effects.