N-methyl-D-aspartic Acid (n-methyl-d-aspartic + acid)

Distribution by Scientific Domains

Selected Abstracts

Effect of exogenous glutamate and N-Methyl-D-aspartic acid on spontaneous activity of isolated human ureter

Slobodan M Jankovic
Objectives: While the neurotransmitter role of glutamate in the gastrointestinal tract has been shown, its effects on smooth muscle of the human ureter have not previously been investigated. In our study we have investigated the effects of exogenous glutamate on the spontaneous activity of isolated human ureter, taken from 14 adult patients after nephrectomy. Methods: The segment of ureter, excised 3 cm distal from the pyeloureteral junction, was isolated in an organ bath. Both longitudinal tension and intraluminal pressure of the segment were recorded simultaneously. Results: Glutamate administered in the lumen of the isolated ureteral segments (7.8 10,7 M/L,3.5 10,2 M/L) was ineffective. When added to the isolated organ bath from the serous side of the ureteral segment, glutamate (7.9 10,6 M/L,10.6 10,3 M/L) and N-Methyl-D-aspartic acid (NMDA) (9.1 10,8 M/L,3.1 10,5 M/L) produced a concentration-dependent increase in spontaneous activity of the isolated preparations, while kainic acid (6.3 10,8 M/L,10.5 10,5 M/L) and (+/,)- trans -1-Aminocyclopentane- trans -1,3-dicarboxylic acid (ACPD) (7.7 10,8 M/L ,6.5 10,5 M/L) were ineffective. Conclusions: The results of our study suggest that an excitatory neurotransmitter glutamate stimulates spontaneous activity of the human ureter through activation of NMDA ionotropic receptors, located on smooth muscle cells or intramural nerve fibers [source]

Analgesic effect of dextromethorphan in neuropathic pain

K. C. Carlsson
Background: Dextromethorphan, a clinically available N-methyl-D-aspartic acid (NMDA) receptor antagonist, has an analgesic effect in patients with diabetic neuropathy. The aim of this study was to evaluate the analgesic and adverse effects of a single high dose of dextromethorphan on spontaneous pain in patients suffering long-term neuropathic pain of traumatic origin. Methods: Fifteen patients with post-traumatic neuropathic pain participated in this placebo-controlled, double-blind, randomized crossover study. On two separate occasions, the participants received 270 mg of dextromethorphan hydrobromide or placebo. Pain intensity, adverse effects and serum concentrations of dextromethorphan and metabolites were registered. Results: Dextromethorphan had a statistically significant analgesic effect compared with placebo, but the effect varied markedly among the patients. Light-headedness was the most important adverse effect reported. Extensive metabolizers of dextromethorphan had an apparently better analgesic effect than poor metabolizers. Conclusion: This report indicates that a single high dose of dextromethorphan has an analgesic effect in patients with neuropathic pain of traumatic origin. The main metabolite dextrorphan seems to be important for the analgesic effect. At the relatively high dose studied, the clinical usefulness of dextromethorphan is limited to that portion of the patient population experiencing analgesia without an unacceptable level of adverse effects. [source]

Structure and composition of the postsynaptic density during development

Matthew T. Swulius
Abstract In this study, we used electron tomography as well as immunogold labeling to analyze the morphology and distribution of proteins within postsynaptic densities (PSDs) isolated from rats before birth (embryonic day 19) and at postnatal days 2, 21, and 60. Our data provide direct evidence of distinct morphological and compositional differences in PSDs throughout development. Not all PSD components are present at the early stages of development, with a near lack of the scaffolding molecule PSD-95 at E19 and P2. The presence of NR1 and NR2b suggests that PSD-95 is not directly required for clustering of N-methyl-D-aspartic acid (NMDA) receptors in PSDs early in development. ,-Actinin is abundant by E19, suggesting that it is a core structural component of the PSD. Both , and , isoforms of Ca2+/calmodulin-dependent protein kinase II (CaMKII) are present early on but then rise in labeling density by approximately fourfold by P21. Among all the molecules studied, only calmodulin (CaM) was found in higher abundance early in PSD development and then fell in amount over time. Spatial analysis of the immunogold label shows a nonrandom distribution for all the proteins studied, lending support to the idea that the PSD is systematically assembled in an organized fashion. Morphological data from electron tomography shows that the PSD undergoes major structural changes throughout development. J. Comp. Neurol. 518:4243,4260, 2010. 2010 Wiley-Liss, Inc. [source]

Neuroendocrine regulation of prolactin secretion in adult female rhesus monkeys during different phases of the menstrual cycle: role of neuroexcitatory amino acid (NMA)

S. Jahan
Abstract The present study attempts to examine the role of N-methyl-D, L-aspartate (NMDA) receptors in the central regulation of prolactin (PRL) secretion, which may be involved in ovarian function and its alteration by glutamate in various phases of the menstrual cycle of female rhesus monkeys (Macaca mulatta). The results suggest that the glutaminergic component of the control system, which governs PRL secretion by utilizing NMDA receptors, may have an important role in regulating changes in PRL secretion. The response of PRL during the luteal phase of the cycle was different from that observed in follicular and menstrual phases. Steroids may influence the NMDA-dependent drive to release PRL. N-methyl-D-aspartic acid (NMA) involvement in the regulation of PRL secretion may occur through activation of the PRL-stimulating system depending on the physiological state or steroidal milieu. It is possible, therefore, that the NMA-induced release of PRL-releasing factors (PRF) and PRL are enhanced in the presence of ovarian feedback. Am. J. Primatol. 69:1,12, 2007. 2006 Wiley-Liss, Inc. [source]

Advances in the pathophysiology of status epilepticus

J. W. Y. Chen
Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABAA (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABAA receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, ,spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed. [source]