Ambien online research references









J Chromatogr B Biomed Appl. 1996 Jan 12;675(1):131-7.
Direct determination of zolpidem and its main metabolites in urine using capillary electrophoresis with laser-induced fluorescence detection.

Hempel G, Blaschke G.

Institute of Pharmaceutical Chemistry, University of Munster, Germany.

Zolpidem is a new sleep inducer belonging to the imidazopyridine class. We wish to report a method for the determination of zolpidem and its main metabolites in urine without extraction using capillary electrophoresis with UV laser-induced fluorescence detection with a He-Cd laser. A 10-nl sample of urine can be directly applied to the capillary. The separation is carried out within 10 min, and the limit of detection is 2 ng/ml. This procedure is very simple and fast. No organic solvents are necessary.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8634754&dopt=Abstract

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Eur Neuropsychopharmacol. 1999 Jan;9(1-2):29-35.
The effects of benzodiazepine (triazolam), cyclopyrrolone (zopiclone) and imidazopyridine (zolpidem) hypnotics on the frequency of hippocampal theta activity and sleep structure in rats.

Yoshimoto M, Higuchi H, Kamata M, Yoshida K, Shimizu T, Hishikawa Y.

Department of Neuropsychiatry, Akita University School of Medicine, Akita City, Japan.

In order to investigate the relative efficacy and safety of zopiclone and zolpidem, we compared the effects of higher doses of zopiclone and zolpidem on the frequency of hippocampal theta activity and sleep structure with that of triazolam. Rats were divided into triazolam treatment group (1 mg/kg, 5 mg/kg), zopiclone treatment group (20 mg/kg, 100 mg/kg) and zolpidem treatment group (20 mg/kg, 100 mg/kg). Rats were injected intraperitoneally with these drugs or their vehicle. Polygraphic sleep recording and visual frequency analysis of the hippocampal EEG activity in REM sleep were carried out for 6 h after each injection. Zolpidem, unlike triazolam and zopiclone, had a much milder reducing-effect on the frequency of hippocampal theta activity and suppressing-effect on REM sleep. These results suggest that zolpidem may prove to be a safer hypnotic drug which has fewer or milder side effects than are benzodiazepine and cyclopyrrolone hypnotics.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10082225&dopt=Abstract

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J Chromatogr B Biomed Sci Appl. 1999 Nov 12;734(2):299-305.
Determination of zolpidem in serum microsamples by high-performance liquid chromatography and its application to pharmacokinetics in rats.

Wang Q, Sun L, Lau CE.

Capital University of Medical Sciences, Department of Chemistry, School of Basic Sciences, Beijing, People's Republic of China.

A single-solvent extraction step high-performance liquid chromatographic method is described for quantitating zolpidem in rat serum microsamples (50 microl). The separation used a 2.1 mm I.D. reversed-phase OD-5-100 C18 column, 5 microm particle size with an isocratic mobile phase consisting of methanol-acetonitrile-26 mM sodium acetate buffer (adjusted to pH 2.0 with 40% phosphoric acid) containing 0.26 mM tetrabutylammonium phosphate (13:10:77, v/v/v). The detection limit was 3 ng/ml for zolpidem using an ultraviolet detector operated at 240 nm. The recovery was greater than 87% with analysis performed in 12 min. The method is simple, rapid, and applicable to pharmacokinetic studies of zolpidem after administering two intravenous bolus doses (1 and 4 mg/kg) in rats.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10595727&dopt=Abstract

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J Chromatogr B Biomed Appl. 1996 Jan 12;675(1):43-51.
Simultaneous determination of zolpidem and zopiclone in human plasma by gas chromatography-nitrogen-phosphorus detection.

Stanke F, Jourdil N, Bessard J, Bessard G.

Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, France.

A simple, specific and selective method for the simultaneous determination of zolpidem and zopiclone in human plasma is described. After a liquid-liquid extraction, the extract is injected into a capillary gas chromatograph with an OV-1 fused-silica column coupled to a nitrogen-phosphorus detector. The detection limits are 1 and 2 ng/ml for zolpidem and zopiclone, respectively. The method described is reproducible and linear over a range of concentrations, rendering it suitable for use for pharmacokinetic studies or toxicological evaluations. Absolute identification of the chromatographed compounds is accomplished by gas chromatography--mass spectrometry in both electron-impact and positive-ion chemical ionisation modes.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8634767&dopt=Abstract

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Mol Pharmacol. 1996 Jun;49(6):1080-4.
Point mutations of the alpha 1 beta 2 gamma 2 gamma-aminobutyric acid(A) receptor affecting modulation of the channel by ligands of the benzodiazepine binding site.

Buhr A, Baur R, Malherbe P, Sigel E.

Department of Pharmacology, University of Bern, Switzerland.

Clinically relevant benzodiazepines allosterically stimulate neurotransmitter-evoked chloride currents at the gamma-aminobutyric acid type A(GABAA) receptor. Rat wild-type or mutated alpha 1, beta 2, and gamma 2S subunits were coexpressed in Xenopus oocytes and investigated with electrophysiological techniques. Point mutations in two subunits were identified that affect the response of gamma-aminobutyric acid (GABA)-induced currents by benzodiazepines. Mutation of one of three amino acid residues to alanine (alpha Tyr161 and alpha Thr206) or leucine (gamma Phe77) resulted in a approximately 3-fold increase in potentiation by diazepam. The response to zolpidem was increased in two mutant channels containing the mutated alpha subunit but was nearly absent in channels containing the mutated gamma subunit. In the former cases, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) acted as a negative allosteric modulator of the channel, much stronger than in the wild-type channel, whereas there was no significant difference to the wild-type channel in the latter case. Thus, the mutant gamma subunit has different functional consequences for the various types of ligand of the benzodiazepine binding site. All three amino acid residues, alpha Tyr161, alpha Thr206, and gamma Phe77, are close or identical to homologous residues that are implicated in GABA binding. If the residues binding the channel agonist GABA are located at subunit interfaces, the residues influencing the benzodiazepine effects must also be located at subunit interfaces.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8649346&dopt=Abstract

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