GABAA receptor pharmacology and subtype mRNA expression in human neuronal NT2-N cells. Minimal interaction between fluoxetine and multiple-dose zolpidem in healthy women. Cell death mediated by amino acid transmitter receptors in human alcoholic brain damage: conflicts in the evidence. Ontogeny of altered synaptic function in a rat model of chronic temporal lobe epilepsy. Rapid phase advance of the 24-h melatonin profile in response to afternoon dark exposure. Ambien online references

Ambien online research references

J Neurosci. 1998 Jul 1;18(13):4993-5007.
GABAA receptor pharmacology and subtype mRNA expression in human neuronal NT2-N cells.

Neelands TR, Greenfield LJ Jr, Zhang J, Turner RS, Macdonald RL.

Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48104-1687, USA.

Human NT2 teratocarcinoma cells differentiate into neuron-like NT2-N cells when treated with retinoic acid. GABA evoked concentration-dependent whole-cell currents in NT2-N cells with an EC50 of 21.8 microM and a Hill slope of 1.2. GABAA receptor (GABAR) currents reversed at ECl- and did not display voltage-dependent rectification. GABAR single channels opened in bursts to a 23 pS main conductance level and a 19 pS subconductance level, with infrequent openings to a 27 pS conductance level. Kinetic properties of the main conductance level were similar to other native and recombinant GABAR channels. Diazepam and zolpidem enhanced GABAR currents with moderate affinity, whereas methyl-6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate inhibited GABAR currents. Loreclezole enhanced GABAR currents with high affinity, but furosemide antagonized GABAR currents with low affinity. The neurosteroids alphaxalone and pregnenolone sulfate appropriately modulated GABAR currents. Zinc blocked GABAR currents with low affinity, but lanthanum did not significantly alter NT2-N GABAR currents. Reverse transcription PCR (RT-PCR) performed on RNA from NT2-N cells clearly detected transcripts encoding human alpha2, alpha3, alpha5, beta3, gamma3, and pi subtypes. The combined pharmacological and RT-PCR results are most consistent with a single or predominant GABAR isoform composed of an alpha2 and/or alpha3 subtype combined with the beta3 and gamma3 subtypes. The data do not rule out receptors containing combinations of alpha2 and/or alpha3 subtypes with the alpha5 subtype or receptors with both beta1 and beta3 subtypes. The presence or absence or the pi subunit in functionally expressed receptors could not be determined.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9634565&dopt=Abstract

word search insomnia ambien online literature

Drug Metab Dispos. 1998 Jul;26(7):617-22.
Minimal interaction between fluoxetine and multiple-dose zolpidem in healthy women.

Allard S, Sainati S, Roth-Schechter B, MacIntyre J.

Lorex Pharmaceuticals, Chicago, IL 60680-5110, USA.

The objective was to evaluate possible pharmacokinetic and pharmacodynamic interactions for repeated nightly zolpidem dosing with fluoxetine. Twenty-nine healthy female volunteers (mean age, 25. 6 years) received zolpidem (10 mg) and fluoxetine (20 mg) in the following open design: zolpidem on night 1 followed by 1 washout day, a daily morning dose of fluoxetine on days 3 through 27, and a morning dose of fluoxetine plus an evening dose of zolpidem on days 28 through 32. Plasma levels of zolpidem, fluoxetine, and norfluoxetine were determined at the transitions from one regimen to the next. Morning psychomotor tests were performed on days 1, 2, 28, 29, and 33. Steady-state plasma concentrations of fluoxetine/norfluoxetine were reached by day 24 of fluoxetine dosing. No significant differences in any pharmacokinetic parameters for fluoxetine and norfluoxetine were observed between day 27 and day 32. There were no significant differences in AUC, maximal plasma concentration, or time to maximal concentration parameters for zolpidem plasma concentrations among nights 1, 28, and 32. There was a statistically significantly increased t1/2 for zolpidem on night 32, compared with night 28 (3.64 and 3.29 hr, respectively). There were no significant differences in the next-morning Digit Symbol Substitution Test performance at any time in the study. Both zolpidem and fluoxetine were well tolerated alone or during coadministration. These findings indicate the absence of clinically significant pharmacokinetic or pharmacodynamic interactions between fluoxetine and zolpidem (five consecutive doses) when the drugs are coadministered to healthy women. Therefore, based on these observations, short-term cotherapy with fluoxetine (20 mg) and zolpidem (10 mg) appears safe.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9660843&dopt=Abstract

word search insomnia ambien online literature

Ann N Y Acad Sci. 1998 May 30;844:50-8.
Cell death mediated by amino acid transmitter receptors in human alcoholic brain damage: conflicts in the evidence.

Dodd PR, Lewohl JM.

Clinical Research Laboratory, Royal Brisbane Hospital Research Foundation, Australia.

Human alcoholics have reduced neuronal counts in certain brain regions, such as superior frontal cortex (SFC), where the form and quantity of synaptic gamma-aminobutyric acid type A (GABAA) receptor sites are atypical. We measured the expression of GABAA receptor isoform mRNA and protein, since GABAA receptor pharmacology is strongly influenced by its subunit composition. Cortex samples were obtained at autopsy; whole-tissue extracts were assayed for mRNA by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), while synaptic membranes were studied for both GABAA receptor pharmacology and subunit protein levels by Western blots with isoform-specific antibodies. Although alpha 1 and alpha 3 mRNA species were strongly expressed in alcoholics irrespective of cirrhosis than in controls, alpha 1 protein differed little between case groups, and alpha 3 protein showed some complex variations. Differences in GABAA pharmacology conformed more closely with differences in protein levels than with altered mRNA expression.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9668664&dopt=Abstract

word search insomnia ambien online literature

Brain Res. 1998 Jul 20;799(2):183-96.
Ontogeny of altered synaptic function in a rat model of chronic temporal lobe epilepsy.

Mangan PS, Bertram EH 3rd.

Department of Neurology, Box 394, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.

In the limbic status model of chronic temporal lobe epilepsy, hippocampal stimulation induces acute status epilepticus in rats; recurrent, spontaneous seizures develop following an asymptomatic silent period lasting several weeks. Previous work has shown increased excitability and decreased inhibition in CA1 pyramidal neurons in chronically epileptic animals. To determine the relationship of altered cellular responses to seizure onset, in vitro intracellular recording was used to follow the evolution of changes in synaptic physiology occurring during the seizure-free silent period. Pyramidal cells displayed increasing epileptiform activity throughout the period investigated, 3-14 days following status; the mean number of evoked action potentials from 1.1+/-0.05 in control cells to 2.4+/-0.4 early (3 days after status) and 4. 3+/-0.7 late (14 days) in the silent period. Monosynaptic inhibitory postsynaptic potentials mediated by gamma-aminobutyric acid-A receptors in silent period cells differed markedly from controls. Area, rise time, and duration of these potentials decreased by 40-60% within 3 days following status and to values commensurate with chronically epileptic animals in 7 to 10 days. gamma-Aminobutyric acid-B receptor-mediated IPSPs diminished more gradually in the silent period, reaching a minimum at day 14. In contrast, presynaptic gamma-aminobutyric acid-B receptor function showed maximum impairment 3 days after status. The benzodiazepine type 1 receptor agonist zolpidem reduced hyperexcitability in both silent period and chronically epileptic cells, but was more effective at unmasking the underlying IPSP in silent period neurons. The results indicate that changes in different components of pyramidal cell inhibitory synaptic physiology associated with chronic epilepsy in this model evolve individually at different rates, but are all complete before seizure onset. Although the results do not imply causality, they do suggest that the development of physiological changes in CA1 pyramidal cells may contribute to the lag period preceding the onset of chronic seizures. Copyright 1998 Elsevier Science B.V. All rights reserved.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9675275&dopt=Abstract

word search insomnia ambien online literature

Am J Physiol. 1998 Jul;275(1 Pt 1):E48-54.
Rapid phase advance of the 24-h melatonin profile in response to afternoon dark exposure.

Van Cauter E, Moreno-Reyes R, Akseki E, L'Hermite-Baleriaux M, Hirschfeld U, Leproult R, Copinschi G.

Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.

To investigate the adaptation of melatonin secretion to an abrupt time shift and the effects of sleep facilitation with a hypnotic, eight subjects were submitted to an 8-h advance shift achieved by advancing bedtimes from 2300-0700 to 1500-2300. Each subject participated in two studies (i.e., placebo and zolpidem). Each study included a baseline period with dim light during waking hours and 2300-0700 bedtimes in total darkness. Blood samples for determination of plasma melatonin were obtained at 20-min intervals for 68 h. Advanced exposure to sleep and darkness resulted in a nearly 2-h advance of melatonin onset, which appeared within 6 h after lights-out during the first shifted night, and an almost 1-h advance of the melatonin offset. No further adaptation occurred during the second shifted sleep period. Zolpidem had no beneficial effects on the adaptation of the melatonin profile. There was no relationship between sleep parameters and the magnitude of the melatonin shifts. Thus the overall advance of melatonin profiles was primarily achieved during the initial exposure to an 8-h period of darkness. The present data suggest that exposure to dark affects human circadian phase.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9688873&dopt=Abstract

word search insomnia ambien online literature

DreamPharm: Herbal and Nutritional supplements online || Hair Million herbal formula for hair loss and hair growth || Wellstreet online pharmacy for click-order prescription medications || Altace Online Pharmacy || Rx Drugs USA, Prescription Drugs Online Pharmacy || Insurance plans and information || Insurance policies for all purposes || Antibiotics and prescription medications online literature ||