Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new ambien research articles will be listed here shortly after becoming available to us.
Related Sponsors
Medical research on ambien
Successful treatment of the Meige syndrome with oral zolpidem monotherapy.
Mov Disord. 2008 Jun 25;
An JY, Kim JS, Kim YI, Lee KS
Int J Clin Exp Hypn. 2008 Jul; 56(3): 270-80
Abramowitz EG, Barak Y, Ben-Avi I, Knobler HY
This study evaluated the benefits of add-on hypnotherapy in patients with chronic PTSD. Thirty-two PTSD patients treated by SSRI antidepressants and supportive psychotherapy were randomized to 2 groups: 15 patients in the first group received Zolpidem 10 mg nightly for 14 nights, and 17 patients in the hypnotherapy group were treated by symptom-oriented hypnotherapy, twice-a-week 1.5-hour sessions for 2 weeks. All patients completed the Stanford Hypnotic Susceptibility Scale, Form C, Beck Depression Inventory, Impact of Event Scale, and Visual Subjective Sleep Quality Questionnaire before and after treatment. There was a significant main effect of the hypnotherapy treatment with PTSD symptoms as measured by the Posttraumatic Disorder Scale. This effect was preserved at follow-up 1 month later. Additional benefits for the hypnotherapy group were decreases in intrusion and avoidance reactions and improvement in all sleep variables assessed.
Neuropsychopharmacology. 2008 Jun 18;
Heikkinen AE, Möykkynen TP, Korpi ER
Initial effects of drugs of abuse seem to converge on the mesolimbic dopamine pathway originating from the ventral tegmental area (VTA). Even after a single dose, many drugs of abuse are able to modulate the glutamatergic transmission activating the VTA dopamine neurons, which may represent a critical early stage in the development of addiction. Ligands acting on the benzodiazepine site of the inhibitory gamma-aminobutyric acid type A (GABA(A)) receptors are known to be rewarding in animal models and have abuse liability in humans, but notably little evidence exists on the involvement of the mesolimbic dopamine system in their effects. Here we report that single in vivo doses of benzodiazepine-site agonists, similar to morphine and ethanol, induce a modulation in the glutamatergic transmission of VTA dopamine neurons. This is seen 24 h later as an increase in the ratio between alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated excitatory currents using whole-cell patch-clamp configuration in mouse VTA slices. The effect was due to increased frequency of spontaneous miniature AMPA receptor-mediated currents. It lasted at least 3 days after the injection of diazepam, and was prevented by coadministration of the benzodiazepine-site antagonist flumazenil or the NMDA receptor antagonist dizocilpine. A single injection of the GABA(A) receptor alpha1 subunit-preferring benzodiazepine-site ligand zolpidem also produced an increase in the AMPA/NMDA ratio in VTA dopamine neurons. These findings suggest a role for the mesolimbic dopamine system in the initial actions of and on neuronal adaptation to benzodiazepines.Neuropsychopharmacology advance online publication, 18 June 2008; doi:10.1038/npp.2008.89.
J Psychopharmacol. 2008 Jun 18;
Bailey JE, Papadopoulos A, Seddon K, Nutt DJ
Abstract Studies in human volunteers that can demonstrate proof of concept are attractive in that possible mechanisms and potential new drug treatments can be examined. We have been developing models of anxiety disorders using the inhalation of 7.5% CO2 for 20 min to model generalised anxiety disorder, as well as using the previously reported 35% CO2 as a model for panic anxiety. In a double-blind, placebo-controlled, three-way crossover study in 12 healthy volunteer subjects, we compared a full agonist at the benzodiazepine receptor that binds to four alpha-subtypes of the receptor (alpha-1,-2,-3,-5) (alprazolam 1 mg), with zolpidem (5 mg), an agonist selective for the alpha-1 subtype of the gamma amino butyric acid-receptor subtype A (GABA-A) receptor, which is a widely used hypnotic drug. Compared with placebo, both drugs significantly attenuated peak CO2-induced changes in subjective feelings after the inhalation of 7.5% CO2 for 20 min. However, there were fewer significant differences after a single vital capacity inhalation of 35% CO2, where zolpidem was less efficacious than alprazolam at reducing CO2-induced symptoms. In conclusion, our results show that zolpidem shows some anxiolytic efficacy in the 7.5% CO2 model, similar to alprazolam, and this is the first report of such an effect of zolpidem in a model of anxiety. These and other studies of benzodiazepines in clinical and volunteer studies suggest a definite role of the GABA-A receptor in CO2-induced anxiety, and it would be of interest to examine other GABA-A receptor subtype selective drugs, which are now in early phase clinical studies and are showing selective efficacy in pharmacodynamic studies.
Neuropharmacology. 2008 May 9;
Auta J, Impagnatiello F, Kadriu B, Guidotti A, Costa E
Whereas advances in the molecular biology of GABA(A) receptor complex using knock-out and knock-in mice have been valuable in unveiling the structure, composition, receptor assembly, and several functions of different GABA(A) receptor subtypes, the mechanism(s) underlying benzodiazepine (BZ) tolerance and withdrawal remain poorly understood. Studies using specific GABA(A) receptor subunit knock-in mice suggest that tolerance to sedative action of diazepam requires long-term activation of alpha1 and alpha5 GABA(A) receptor subunits. We investigated the role of long-term activation of these GABA(A) receptor subunits during anticonvulsant tolerance using high affinity and high intrinsic efficacy ligands for GABA(A) receptors expressing the alpha5 subunit (imidazenil) or alpha1 subunit (zolpidem), and a non-selective BZ recognition site ligand (diazepam). We report here that long-term activation of GABA(A) receptors by zolpidem and diazepam but not by imidazenil elicits anticonvulsant tolerance. Although anticonvulsant cross-tolerance occurs between diazepam and zolpidem, there is no cross-tolerance between imidazenil and diazepam or zolpidem. Furthermore, diazepam or zolpidem long-term treatment decreased the expression of mRNA encoding the alpha1 GABA(A) receptor subunit in prefrontal cortex by 43% and 20% respectively. In addition, diazepam but not zolpidem long-term treatment produced a 30% increase in the expression of the alpha5 GABA(A) receptor subunit mRNA in prefrontal cortex. In contrast, imidazenil which is devoid of anticonvulsant tolerance does not elicit significant changes in the expression of alpha1 or alpha5 GABA(A) receptor subunit. These findings suggest that long-term activation of GABA(A) receptors containing the alpha1 or other subunits but not the alpha5 receptor subunit is essential for the induction of anticonvulsant tolerance.
Drug screening of hair by liquid chromatography-tandem mass spectrometry.
J Anal Toxicol. 2008 Jun; 32(5): 364-72
Hegstad S, Khiabani HZ, Kristoffersen L, Kunøe N, Lobmaier PP, Christophersen AS
Hair has become an important matrix for drug analysis, complementary to blood and urine as a matrix. A prolonged detection window makes hair analysis suitable for the detection of exposure to illegal and medicinal drugs for periods up to 12 months. In the present study, a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for drug screening in hair was developed and validated. To 20 mg of hair, 0.45 mL of acetonitrile/25 mM formic acid (5:95 v/v) and 50 microL of deuterated internal standards were added, and the sample was incubated in a water bath at 37 degrees C for 18 h. LC separation was achieved with a Zorbax SB-Phenyl column (2.1 x 100 mm, 3.5-microm particle). Mass detection was performed by positive ion mode electrospray LC-MS-MS and included the following drugs/metabolites: nicotine, cotinine, morphine, 6-monoacetylmorphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymeth-amphetamine, cocaine, benzoylecgonine, 7-aminonitrazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, oxazepam, diazepam, alprazolam, zopiclone, zolpidem, carisoprodol, meprobamate, buprenorphine, and methadone. Within- and between-assay relative standard deviations varied from 2.0% to 12% and 2.7% to 15%, respectively. The accuracies were in the range of -24% to 16%, and recoveries ranged from 25% to 100%. The LC-MS-MS method proved to be simple and robust for the determination of drugs in hair. It has been used for authentic samples in our laboratory in the past year.
J Biomol Struct Dyn. 2008 Aug; 26(1): 57-64
Chen CY, Chen YF, Tsai HY
The reliable structure of gamma aminobutyric acid type A (GABA-A) receptor was built based on several criteria. According to zolpidem and GABA binding conformations, the key residues that were indicated to be the determination of binding were consistent with our simulation. Investigation of the major effective constituents from suanzaoren to modulate the GABA-A was the aim of the study. Jujuboside A, which was indicated to be the effective constituent from suanzaoren, had no blood-brain barrier (BBB) penetration and was unable to bind at both binding sites due to its large volume. In addition, the glycoside groups on jujuboside A were easily to be hydrolyzed. In contrast, jujubogenin, which was hydrolyzed from jujuboside A, had the most compatible binding conformation. In addition, jujubogenin formed two HBs with the key residue beta(2)-Thr226 and beta(2)-Tyr229 at the GABA binding site. Moreover, it gained the comparably highest scoring values among suanzaoren constituents. Furthermore, the Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) descriptor predicted that jujubogenin have good BBB penetration. Consequently, we suggested jujubogenin to be the effective suanzaoren constituent to mediate the GABA-A receptor.
Am J Psychiatry. 2008 Jun; 165(6): 678-86
Buysse DJ
Zolpidem extended-release in the long-term treatment of insomnia.
Nat Clin Pract Neurol. 2008 May 20;
Neubauer DN
Zolpidem improves akinesia, dystonia and dyskinesia in advanced Parkinson's disease.
J Clin Neurosci. 2008 May 14;
Chen YY, Sy HN, Wu SL