Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.
Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.
Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm. 相似文献
INTRODUCTION As early as 1969 we started a program to develop two-dimensional real-time ultrasonic imaging. As a result, the first real-time images of the heart were made visible with the linear array in 1971 (1) .Parallel to the development of this nonin- vasive method for observation of the heart,a study on invasive cardiac observation was 相似文献
IL-12:Interleikin-12(IL-12)was discovered as a cytokine with aunique heterodimeric structure.It was originally found in cultere su-pematant from B lymphobastoid cell lines as natural killer cell stimu-latory factor by M.Kobayashi,et al.in 1989.Recent studies haveshown that the majority of IL-12 is produced by macrophages/mono-cytes following appropriate stimulation.IL-12 Palys a pivotal role inthe regulation of cell-mediated immunity,exerting pleiotropic effectson T cells and natural killer cells.This function is promoted by theIL-12 induced production of interferon-γ from both resting and acti-vated NK and T cells,by the proliferative activity of IL-12 on acti-vated NK and T cells,by enhancing the cytotoxic activity of NKcells,and by supperting cytotoxic T lymphocyte generation.IL-12also promotes the development of naive murine CD4~ T cells into Thelper type 1(Th1)cells in response to antigen.Based on thesepotent immunomodulatory activities,IL-12 has been shown to havetherapeutic activity in a variety 相似文献
Background: General anesthetics inhibit evoked release of classic neurotransmitters. However, their actions on neuropeptide release in the central nervous system have not been well characterized.
Methods: The effects of representative intravenous and volatile anesthetics were studied on the release of sulfated cholecystokinin 8 (CCK8s), a representative excitatory neuropeptide, from isolated rat cerebrocortical nerve terminals (synaptosomes). Basal, elevated KCl depolarization-evoked and veratridine-evoked release of CCK8s from synaptosomes purified from rat cerebral cortex was evaluated at 35[degrees]C in the absence or presence of extracellular Ca2+. CCK8s released into the incubation medium was determined by enzyme-linked immunoassay after filtration.
Results: Elevation of extracellular KCl concentration (to 15-30 mm) or veratridine (10-20 [mu]m) stimulated Ca2+-dependent CCK8s release. Basal, elevated KCl- or veratridine-evoked CCK8s release was not affected significantly by propofol (12.5-50 [mu]m), pentobarbital (50 and 100 [mu]m), thiopental (20 [mu]m), etomidate (20 [mu]m), ketamine (20 [mu]m), isoflurane (0.6-0.8 mm), or halothane (0.6-0.8 mm). 相似文献
