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991.
Epilepsy is characterized by neuronal hyperexcitability and hypersynchronization. Disruption of electroencephalographically (EEG) synchronized epileptiform discharges may be a possible therapy for epilepsy. In the present study, to clarify the role of EEG desynchronization on epilepsy, we investigated the effect of modafinil, a potent wake-promoting substance with EEG desynchronization activity, on epilepsy in mice and clarified the receptors involved in the suppression of seizure caused by maximal electroshock (MES) and pentylenetetrazol (PTZ) kindling models. Modafinil given at 22.5, 45, and 90 mg/kg, i.p. significantly decreased the incidence of tonic hindleg extension in MES seizure models, and protected against PTZ-induced convulsive behaviors in a dose-dependent manner. In addition, modafinil at 180 mg/kg exerted an antiepileptic effect in the MES model; however, at the same dosage it increased the seizure stage in the PTZ-kindling model. The antiepileptic effect in both MES and PTZ models was antagonized by the adrenergic alpha(1) receptor antagonist terazosin, but not by the adrenergic alpha(2) receptor antagonist yohimbine or by dopaminergic receptor antagonists, SCH-23390 (for D(1) receptors) and haloperidol (for D(2) ones). Pyrilamine, a histaminergic H(1) receptor antagonist, counteracted the antiepileptic action of modafinil in the PTZ induced-kindling model, but not in the MES seizure model. Taken together, the present findings indicate that modafinil exerted its antiepileptic effect via adrenergic alpha(1) and histaminergic H(1) receptors, and might be of potential use in the treatment of epilepsy. 相似文献
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Tan JJ Liu C Sun XH Cong XJ Hu LM Wang CX Liang XJ 《Mini reviews in medicinal chemistry》2012,12(9):875-889
HIV-1 integrase (IN) is a crucial enzyme in the life cycle of HIV-1 and also a validated target for developing anti-HIV inhibitors. Recent progress in drug design has significantly accelerated the development of anti-AIDS IN inhibitors. A large amount of novel inhibitors that interact specifically with IN were developed along with the expanding and application of methods to drug design. This article reviewed the anti-HIV IN inhibitors discovered by the rational drug design approaches in the recent 5-year. 相似文献
998.
为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂,设计并合成了一系列5-溴-,5-甲基-,和5-未取代的3-硝基-1,2,4-三唑-1-乙酰胺类化合物,用HeLaS3细胞进行了体外试验。结果表明5-溴取代衍生物的增敏作用强于相应的5-甲基-或5-未取代的硝基三唑衍生物,但是它们的毒性亦增大。修饰1位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中TA-101[2-(3-硝基-1-三唑基)乙酰胺]由于有高的增敏作用和低亲脂性,可能是一个有希望的放射增敏剂。 相似文献
999.
Relative 2-deoxyglucose (2-DG) uptake was investigated during pentobarbital and/or ketamine anesthesia, when animals were either kept in silence or stimulated with wide band noise at 85 dB SPL. In the absence of anesthesia, noise stimulation produced a large increase in relative 2-DG uptake, when compared to silence, in all auditory nuclei up to and including the inferior colliculus. Much more modest noise-induced increases were seen in the medial geniculate nucleus and auditory cortex. These effects were markedly altered by anesthesia. Pentobarbital, and especially pentobarbital plus ketamine, enhanced stimulus-evoked increases in relative 2-DG uptake in lower auditory nuclei: the cochlear nuclei, superior olivary complex and ventral nucleus of the lateral lemniscus. At the same time, stimulus-evoked increases were decreased in the dorsal nucleus of the lateral lemniscus and inferior colliculus, and virtually eliminated in the medial geniculate and auditory cortex. The results of this study permit more meaningful comparison of 2-DG techniques with electrophysiological measures of central auditory activity, and illuminate the utility and limitations of each method. The data indicate that 2-DG observations from barbiturate-anesthetized preparations should be interpreted with some caution. They further suggest that the 2-DG technique is inappropriate for the study of stimulus-evoked activity in the medial geniculate and auditory cortex of barbiturate-anesthetized animals. 相似文献
1000.
Otospongiosis-like lesions were induced in rats by immunizing them with type II collagen. After seven months' immunization, the rats were killed and processed for histologic study. We found otospongiotic lesions in the bony cochlea, vestibule, semicircular canal, and in the regions near the oval window and round window. The spongiotic lesions in the otic capsules were similar to human otospongiosis and were characterized by the following types of microscopic appearances. 1) The classic type showed enlarged vascular spaces with congestion, macrophages, fibroblasts, and sometimes osteoclasts. 2) The fibrotic type showed vascular spaces filled with fibrous tissues. 3) The osteoporotic type had a porous appearance and was devoid of content. 4) The sclerotic type showed bone spaces partially or entirely being replaced by new bone with blue mantles and a mosaic appearance. Some spongiotic lesions showed a mixture of the above types. The findings suggest that this animal model may provide important information to help understand the process of human otosclerosis. 相似文献