Ambien online research references
Neuroscience. 1995 Feb;64(4):1113-28.
Distribution of [3H]zolpidem binding sites in relation to messenger RNA encoding the alpha 1, beta 2 and gamma 2 subunits of GABAA receptors in rat brain.
Duncan GE, Breese GR, Criswell HE, McCown TJ, Herbert JS, Devaud LL, Morrow AL.
Department of Psychiatry, University of North Carolina at Chapel Hill 27599, USA.
Localization of the messenger RNAs that encode the alpha 1, beta 2 and gamma 2 subunits of GABAA showed a distinct topographic pattern in rat brain which corresponded with [3H]zolpidem binding in most brain regions. The close topographic correspondence between the specific receptor subunits examined and the distribution of [3H]zolpidem binding sites provides support for the hypothesis that this benzodiazepine type 1 selective ligand binds to a GABAA receptor that consists of alpha 1, beta 2 and gamma 2 subunits in the rat brain. Brain regions with relatively high densities of alpha 1, beta 2 and gamma 2 subunits of GABAA and [3H]zolpidem binding included olfactory bulb, medial septum, ventral pallidum, diagonal band, inferior colliculus, substantia nigra pars reticulata and specific layers of the cortex. Two areas with low [3H]zolpidem binding and a virtual absence of these GABAA receptor subunit messenger RNAs were the lateral septum and the striatum. In contrast to the discrete pattern observed for alpha 1 and beta 2 subunit messenger RNAs, the gamma 2 subunit messenger RNA was distributed more diffusely in brain. Only the hippocampus, layer 2 of the piriform cortex and the cerebellum showed a strong concentration of the gamma 2 subunit messenger RNA. It was determined with a polymerase chain reaction assay that both long and short variants of the gamma 2 subunit messenger RNAs were present within several of the brain sites selected for examination. Sites with high densities of [3H]zolpidem binding sites had a greater relative abundance of the gamma 2 long splice variant, compared to the gamma 2 short variant. There were some regions that expressed high levels of alpha 1, beta 2 and gamma 2S subunit messenger RNAs but low [3H]zolpidem binding, suggesting that gamma 2 splice variant expression may modulate high-affinity [3H]zolpidem binding. To determine relationships between in vitro [3H]zolpidem binding and functional sensitivity in vivo, interactions between zolpidem and GABA were assessed in brain regions that contained high and low densities of [3H]zolpidem binding sites. In the medial septum, a brain region with a high concentration of [3H]zolpidem binding sites, iontophoretic application of zolpidem enhanced the inhibitory effect of GABA responses on 70% of the neurons examined. In the lateral septum, which contains very low densities of [3H]zolpidem binding sites, neurons were not sensitive to zolpidem enhancement of GABA-induced inhibition. These electrophysiological results demonstrate a correspondence between the regional distribution of [3H]zolpidem binding in vitro and functional sensitivity to the drug in vivo.
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J Neurochem. 1995 Feb;64(2):867-73.
Aging-associated changes in the pharmacological properties of the benzodiazepine (omega) receptor isotypes in the rat hippocampus.
Ruano D, Benavides J, Machado A, Vitorica J.
Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, Spain.
The aging-associated changes in hippocampal benzodiazepine (omega) receptor isotypes have been investigated in rats of the Wistar and Fischer 344 strains. Displacement experiments of [3H]flunitrazepam binding by zolpidem demonstrated that in hippocampal membranes from adult (3-month-old) Wistar strain rats, high (type I; omega 1)-, intermediate (type IIM; omega 2)-, and low (type IIL; omega 5)-affinity sites for this imidazopyridine account for 27.1 +/- 7.5, 44.2 +/- 7.5, and 28.8 +/- 5.1%, respectively. In hippocampal membranes from aged (24-month-old) rats of the same strain, the relative abundance of these sites was 42.8 +/- 9.3, 26.3 +/- 4, and 36.0 +/- 5.9%, respectively. In contrast, no significant difference was observed in the whole benzodiazepine (omega) binding site density between adult and aged rats. The increase in type I (omega 1) binding site density in the hippocampus of aged rats was also demonstrated in saturation experiments with [3H]zolpidem. This aging-induced increase in [3H]zolpidem binding was also observed in hippocampal membranes from Fischer 344 rats. Moreover, in both rat strains, GABA induced a greater enhancement of [3H]zolpidem (5 nM) binding to type I (omega 1) sites (GABA shift) in aged than in adult hippocampal membranes. Quantitative autoradiographic analysis of [3H]zolpidem binding to coronal brain sections from adult and aged Fischer 344 rats demonstrated that the aging-associated increases in the density of type I (omega 1) binding sites were restricted to the hippocampus. Moreover, increases in binding density were larger in the dentate gyrus and in the CA2 field than in the CA1 and CA3 fields.
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Boll Soc Ital Biol Sper. 1994 May-Jun;70(5-6):151-7.
Analytical profile of zolpidem.
Seccia S.
Department of Pharmaceutical and Toxicological Chemistry, University of Naples.
The paper present an analytical profile of Zolpidem. The applications of chromatographic methods (HPLC and HPTLC) and non-aqueous titrimetry in the analysis of this drug are described. Partition coefficients at pH 2.0 and 7.4 and absorptivity values have been determined. Reversed phase HPLC and HPTLC systems have been successfully performed utilizing methanol/water mixtures as eluent and octadecylsilane as stationary phase. Acidimetric and alkalimetric methods in non aqueous titrimetry have been applied for quantitative analysis. The suggested procedures are proposed as an effective tool for quality control on pure compound and pharmaceutical formulations.
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Pharmacol Biochem Behav. 1994 Nov;49(3):455-61.
Effects of chronic treatment with triazolam on operant responding in rats.
Cohen C, Sanger DJ.
Synthelabo Recherche (L.E.R.S.), Bagneux, France.
The aims of the present study were to investigate the effect of the benzodiazepine antagonist, flumazenil, on operant responding in rats treated chronically with the short-acting hypnotic triazolam and to study the consequence of chronic triazolam treatment on the time course of effects of triazolam and zolpidem. Zolpidem is an imidazopyridine with a pharmacological and behavioral profile that differs from that of the benzodiazepine hypnotics. Rats were treated with saline or triazolam (1 or 3 mg/kg) twice daily for 5 days and were tested daily 1, 3, 5.5 or 7.5 h after injection. In addition, on the 5th day of chronic treatment all rats were injected with flumazenil (10 mg/kg) 10 min before session. The time course of effects of triazolam and zolpidem was determined after cessation of repeated saline or triazolam treatment. Tolerance to the depressant effect of 1 mg/kg of triazolam developed during long-term administration. Flumazenil decreased operant responding in rats pretreated with triazolam. The effect was statistically significant when rats had received 1 mg/kg of triazolam 3 h before the session or 3 mg/kg of triazolam 3, 5.5 or 7.5 h before the session. After cessation of chronic treatment, rats pretreated chronically with 3 mg/kg of triazolam displayed decreased sensitivity to triazolam and to 10 mg/kg but not 3 mg/kg of zolpidem. The present results indicate that chronic treatment with triazolam induces tolerance to the rate-decreasing effect of the drug and dependence as measured by flumazenil-induced disruption of operant responding. The limited degree of cross-tolerance between zolpidem and triazolam may suggest that their pharmacological mechanisms of action are distinct.
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J Pharmacol Exp Ther. 1999 Dec;291(3):932-42.
Antagonist-induced reversal of functional and structural measures of hippocampal benzodiazepine tolerance.
Tietz EI, Zeng XJ, Chen S, Lilly SM, Rosenberg HC, Kometiani P.
Department of Pharmacology, Medical College of Ohio, Toledo, Ohio 43614-5804, USA. etietz
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