Ambien online research references
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One week oral flurazepam (FZP) administration in rats results in anticonvulsant tolerance in vivo, tolerance measured in vitro in hippocampal CA1 pyramidal cells, and regulation of hippocampal gamma-aminobutyric acid(A)-receptor subunit protein expression. A single injection (4 or 20 mg/kg i.p) of the benzodiazepine antagonist flumazenil (FLM) was given 1 day after FZP treatment, and tolerance and subunit protein expression were evaluated 1 day later. In vivo tolerance was measured by a reduced ability of the alpha(1)-subunit-selective agonist zolpidem to suppress pentylenetetrazole-induced seizures. This tolerance was reversed by 20 but not 4 mg/kg FLM. In in vitro hippocampal slices, there was tolerance to the effect of zolpidem to prolong the decay of pyramidal cell miniature inhibitory postsynaptic currents, which was reversed by FLM (4 mg/kg) pretreatment. A reduction in miniature inhibitory postsynaptic current amplitude ( approximately 50%) was also restored by FLM injection. [(3)H]Zolpidem binding measured 0, 2, and 7 days after FZP treatment was significantly decreased in the hippocampus and cortex at 0 days but not thereafter. Changes in alpha(1)- and beta(3)-subunit protein expression were examined via quantitative immunohistochemical techniques. alpha(1)-Subunit protein levels were down-regulated in the CA1 stratum oriens and beta subunit levels were up-regulated in the stratum oriens and stratum radiatum of the CA3 region. Chronic FZP effects on alpha(1)- and beta(3)-subunit protein levels were also reversed by prior FLM injection. FLM's effect on both functional and structural correlates of benzodiazepine tolerance suggests that each of these measures plays an interdependent role in mediating benzodiazepine tolerance.
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Arzneimittelforschung. 1994 Jul;44(7):799-802.
Screening, identification and determination of the two new hypnotics zolpidem and zopiclone.
Ahrens B, Schutz H, Seno H, Weiler G.
Institut fur Rechtsmedizin, Universitat Giessen.
This article reports basic analytical data for screening and detection of the hypnotics zolpidem (CAS 82626-48-0) and zopiclone (CAS 43200-80-2) by using corrected hR-values, GC (gas chromatography) retention indices, UV solvent spectra and remission spectra. Beside this a HPTLC (high-performance thin-layer chromatography)-procedure for quantification is described.
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Fortschr Med. 1994 Sep 10;112(25):344-6.
[Treatment of sleep disorders in the elderly with zolpidem. Results of sleep polygraphy in 3 elderly patients with depressive neuroses]
[Article in German]
Kummer J, Gundel L.
Gerontopsychiatrische Abteilung, Landesklinik Nordschwarzwald, Calw-Hirsau.
Three elderly patients with depressive neuroses and sleep disorders were treated over a period of 20 days with a nocturnal dose of 10 mg zolpidem, a new type of hypnotic. Prior to treatment, after 1 and after 20 days, as well as on the first post-treatment day, polygraphic studies were made during sleep. In addition, vigilance was tested using the Quatember and Maly tests, and diurnal wellbeing checked by means of a questionnaire. The polygraphic results revealed that all major sleep parameters improved under treatment and that no rebound occurred on the first post-treatment day. No negative effects on diurnal wellbeing were registered.
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Int J Dev Neurosci. 1994 Jun;12(4):299-314.
Coincidental appearance of the alpha 1 subunit of the GABA-A receptor and the type I benzodiazepine receptor near birth in macaque monkey visual cortex.
Hendrickson A, March D, Richards G, Erickson A, Shaw C.
Department of Biological Structure, University of Washington, Seattle 98195.
The expression of subtypes of the GABA-A/benzodiazepine receptor complex has been studied during pre- and postnatal development of Macaca monkey visual cortex using complementary radioligand and immunocytochemical labeling. Type I benzodiazepine receptors were labeled directly by [3H]zolpidem. Type II receptors were determined by the amount of binding for [3H]flunitrazepam (FZ) persisting in the presence of the type I-specific ligand CL218872. Monoclonal antibody bd24 was used to label alpha 1 subunits and bd17 to label beta 2 and beta 3 subunits of the GABA-A receptor. Radioligand binding data and bd17 immunoreactivity indicated that type II benzodiazepine receptors were present by fetal day (Fd) 74 (44% of gestation). Immunoreactivity for the beta 2/beta 3 subunits increased until 3-6 weeks after birth, and then declined somewhat into adulthood. Neither radioligand labeling for type I receptors nor immunocytochemical staining for the alpha 1 subunit were apparent until mid-gestation. Both markers appeared shortly before birth in layer 4C, and then in other cortical layers after birth. Immunoreactivity for the alpha 1 subunit increased steadily after birth until it became more intense than that for beta 2/3 subunits in the adult. Quantitative densitometry of CL218872 competition for [3H]FZ binding showed that type I/II distribution was 22%/78% at Fd103; 42%/58% at Fd131; 67%/33% at 9 months; and 61%/39% in adult visual cortex. This "switch" between benzodiazepine receptor subtypes overlaps the postnatal critical period for geniculostriate development, suggesting that the change from type II to type I receptors and the appearance of alpha 1 subunits may play a decisive role in the maturation of geniculocortical axon terminations and cortical response properties. It remains to be shown whether this "switch" is dependent on functional visual input.
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Acta Neurol (Napoli). 1994 Jun;16(3):79-86.
Interleukin-1 beta plasma secretion during diurnal spontaneous and induced sleeping in healthy volunteers.
Covelli V, D'Andrea L, Savastano S, Valentino R, Tommaselli AP, Selleri A, Massari F, Lombardi G.
Chair of Neurology I, Medical School University Federico II, Naples, Italy.
We previously reported nocturnal plasma IL-1 beta (beta) increases during sleep in absence of stress-induced activation of hypothalamic-pituitary-adrenal (HPA) axis. In this paper we evaluate the presence of plasma IL-1 beta secretion in nine healthy volunteers (mean age 31.2 +/- 4.2) during post-prandial naps, after the administration of zolpidem, a benzodiazepine receptorial agonist. Although a significant increase in IL-1 beta plasma levels during spontaneous sleep was present in only four subjects when compared to those obtained during wake and induced-sleep, spontaneous sleep IL-1 beta mean plasma levels appeared slightly higher than both wake and induced-sleep values. Moreover, a negative correlation was present between IL-1 beta and cortisol (F) values obtained during the early afternoon (r = 7; p < 0.05). Our findings are consistent with a possible association of IL-1 beta secretion to physiologic sleep also during daytime spontaneous naps, with the presence of F influence on this phenomenon, and with the lack of IL-1 beta association to daytime naps after sleep-inducer pharmacological agents.
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