Ambien online research references









J Pharmacol Exp Ther. 1992 Oct;263(1):298-303.
Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem.

Perrault G, Morel E, Sanger DJ, Zivkovic B.

Synthelabo Recherche (L.E.R.S.), Bagneux, France.

Zolpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]. The present study investigated whether tolerance and physical dependence develop after repeated treatment with zolpidem as is observed with benzodiazepines. Mice were given zolpidem or the benzodiazepine midazolam (2 x 30 mg/kg, p.o.) for 10 consecutive days. Tolerance to central depressant effects (evaluated by recording spontaneous locomotor activity) and to anticonvulsant effects (measured against pentylenetetrazole-, electroshock- and isoniazid-induced convulsions) was assessed 42 hr after the last administration. A decrease in the latency to isoniazid-induced convulsions was taken as an index of physical dependence and was evaluated 3, 6, 14, 24, 42 and 67 hr after the end of chronic drug treatment. Repeated treatment with midazolam produced tolerance to its sedative and anticonvulsant activities as indicated by shifts of the dose-response curves by a factor of 3 to 5. Fourteen hr after discontinuation of treatment, spontaneous withdrawal was observed and lasted 3 days. When flumazenil was given 3 or 6 hr after the final midazolam injection, precipitated withdrawal was observed. In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects. Moreover, neither spontaneous nor flumazenil-induced precipitated withdrawal was observed in zolpidem-treated mice.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1403792&dopt=Abstract

word search insomnia ambien online literature





J Chromatogr. 1992 Oct 23;581(2):237-50.
Determination of zolpidem, a new sleep-inducing agent, and its metabolites in biological fluids: pharmacokinetics, drug metabolism and overdosing investigations in humans.

Ascalone V, Flaminio L, Guinebault P, Thenot JP, Morselli PL.

Synthelabo Recherche (L.E.R.S.), Department of Clinical Research, Limito, Italy.

For the determination of zolpidem, a new sleep inducer, and its metabolites in human plasma and urine, three methods were developed that are suitable for pharmacokinetics, drug metabolism and overdosing investigations. The methods used for pharmacokinetic and drug metabolism studies are based on column-switching high-performance liquid chromatography; they do not require any sample manipulation because the plasma or diluted urine is injected into a pre-column where clean-up and preconcentration take place. The analytes are transferred by valve-switching to the C18 analytical column for chromatography. To investigate overdose cases, urine samples only are used: the method is simple, because the diluted urine can be injected directly into the analytical column (phenyl type). This allows the identification and quantification of the principal urinary metabolite of zolpidem, the unchanged drug being practically undetectable. All the methods use fluorescence detection, which affords high sensitivity and selectivity. It is necessary to use a method capable of the determination of metabolites even if these are apparently pharmacologically inactive, because in different physiopathological populations the qualitative and quantitative metabolic profiles of zolpidem could be different. The method designed for the investigation of (accidental or deliberate) overdose cases is, as required on such occasions, simple and rapid, with good selectivity with respect to commonly prescribed psychotropic drugs.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1452614&dopt=Abstract

word search insomnia ambien online literature





J Pharm Biomed Anal. 2003 Oct 15;33(3):393-401.
Determination of zolpidem hemitartrate by quantitative HPTLC and LC.

El Zeany BA, Moustafa AA, Farid NF.

Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, 23 El-ahrar St, Cairo, Egypt.

Two methods are described for the determination of zolpidem hemitartrate in presence of its degradation product. The first method was a TLC-UV densitometric one in which the mobile phase methanol: water (20:80) was used for developing the TLC plates. The R(f) of zolpidem hemitartrate was found to be 0.29+/-0.01 and that of its degradation product was 0.59+/-0.01. Linearity range was 0.5-4 microg/spot with mean recovery percentage (99.98+/-0.988)%. The second method was an HPLC method. HPLC was performed on a Bondapack C(18) column. The mobile phase was composed of a mixture of acetonitrile-0.01 M KH(2)PO(4) (40:60). The pH was adjusted to 3.5+/-0.1. Flow rate was 1.2 ml/min. Calibration graphs were linear in the range of 0.5-5 microg/ml with UV detection at 245 nm. Both methods have been successfully applied to pharmaceutical formulations. The results obtained were statistically compared with those obtained by applying the reported methods.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14550858&dopt=Abstract

word search insomnia ambien online literature





J Neurosci. 1999 Aug 15;19(16):7057-65.
GABA(A) receptors expressed in undifferentiated human teratocarcinoma NT2 cells differ from those expressed by differentiated NT2-N cells.

Neelands TR, Zhang J, Macdonald RL.

Graduate Program in the Neurosciences, University of Michigan Health Sciences Center, Ann Arbor, Michigan 48104-1687, USA.

During CNS development, changes occur in expression of GABA(A) receptor subunit subtypes and GABA(A) receptor pharmacological and biophysical properties. We used reverse transcription PCR and whole-cell-recording techniques to determine whether GABA(A) receptor expression and function also changed during retinoic acid-induced differentiation of human Ntera 2 (NT2) teratocarcinoma cells into neuron-like cells (NT2-N cells). In undifferentiated NT2 cells only alpha5, beta3, gamma3, and pi subtype mRNAs were detected. NT2 GABA(A) receptor currents had a maximal amplitude of 52 pA and an EC(50) of 4.0 microM, were relatively insensitive to enhancement by zolpidem and diazepam, and were enhanced by loreclezole and inhibited by lanthanum, zinc, and furosemide. In contrast, in NT2-N cells after 13 weeks of retinoic acid treatment, all GABA(A) receptor subtype mRNAs were detected. Maximal peak whole-cell currents were approximately 50-fold larger than NT2 cell currents, and the GABA EC(50) was higher (39.7 microM). In 13 week NT2-N cells, diazepam, zolpidem, loreclezole, and lanthanum had only small effects on GABA(A) receptor currents, and the zinc IC(50) for current inhibition was significantly higher than that for NT2 cells. In a previous study, we showed that NT2-N cells after 5 weeks of retinoic acid treatment had moderate peak currents, GABA EC(50,) and zinc IC(50) but that currents were robustly enhanced by diazepam, zolpidem, and loreclezole. During differentiation of NT2 cells to NT2-N cells, GABA(A) receptors underwent changes in subunit expression and pharmacology that were similar to many of the developmental changes in GABA(A) receptors that occur in CNS neurons.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10436060&dopt=Abstract

word search insomnia ambien online literature





Neuropharmacology. 2003 Dec;45(7):907-17.
Valproate modifies spontaneous excitation and inhibition at cortical synapses in vitro.

Cunningham MO, Woodhall GL, Jones RS.

Department of Physiology and MRC Centre for Synaptic Plasticity, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.

The anticonvulsant, valproic acid (VPA), has a very wide spectrum of clinical activity and has conventionally been considered to act by enhancing inhibitory GABAergic activity, either by increasing GABA levels and its subsequent release or by enhancing postsynaptic GABA responses. However, the pharmacology of VPA is complex and other mechanisms may well contribute. In the present study, we examined the effect of the drug on the release of GABA and glutamate at synapses in the rat entorhinal cortex, using the whole-cell patch clamp technique to record spontaneous excitatory (sEPSCs) and inhibitory postsynaptic currents (sIPSCs). VPA reduced the frequency but not the amplitude of both spontaneous sEPSCs and sIPSCs, with a more pronounced effect on the former. However, VPA had no effect on miniature, monoquantal events recorded in the presence of TTX, suggesting that the reduction in release occurred via blockade of Na(+)-channels in the presynaptic neurones. In addition, VPA also prolonged the decay time of sIPSCs, and this effect was occluded by a benzodiazepine agonist, zolpidem. These data suggest that in addition to presynaptic effects on release, VPA can potentiate postsynaptic responses, possibly by interaction with the benzodiazepine regulatory site of the GABA(A) receptor.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14573383&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 ||