Ambien online research references
J Neurochem. 2001 Apr;77(2):445-51.
Identification of amino acid residues responsible for the alpha5 subunit binding selectivity of L-655,708, a benzodiazepine binding site ligand at the GABA(A) receptor.
Casula MA, Bromidge FA, Pillai GV, Wingrove PB, Martin K, Maubach K, Seabrook GR, Whiting PJ, Hadingham KL.
Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, UK.
L-655,708 is a ligand for the benzodiazepine site of the gamma-aminobutyric acid type A (GABA(A)) receptor that exhibits a 100-fold higher affinity for alpha5-containing receptors compared with alpha1-containing receptors. Molecular biology approaches have been used to determine which residues in the alpha5 subunit are responsible for this selectivity. Two amino acids have been identified, alpha5Thr208 and alpha5Ile215, each of which individually confer approximately 10-fold binding selectivity for the ligand and which together account for the 100-fold higher affinity of this ligand at alpha5-containing receptors. L-655,708 is a partial inverse agonist at the GABA(A) receptor which exhibited no functional selectivity between alpha1- and alpha5-containing receptors and showed no change in efficacy at receptors containing alpha1 subunits where amino acids at both of the sites had been altered to their alpha5 counterparts (alpha1Ser205-Thr,Val212-Ile). In addition to determining the binding selectivity of L-655,708, these amino acid residues also influence the binding affinities of a number of other benzodiazepine (BZ) site ligands. They are thus important elements of the BZ site of the GABA(A) receptor, and further delineate a region just N-terminal to the first transmembrane domain of the receptor alpha subunit that contributes to this binding site.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11299307&dopt=Abstract
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Neuropharmacology. 2001 Apr;40(5):717-21.
The acute effects of zolpidem compared to diazepam and lorazepam using radiotelemetry.
Elliot EE, White JM.
Department of Clinical and Experimental Pharmacology, University of Adelaide, SA 5005, Australia. eelliot
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intra.nida.nih.gov
The present study used a radiotelemetric method to compare the muscle relaxant, hypothermic and locomotor depressant actions of the imidazopyridine zolpidem, with those of the benzodiazepines lorazepam and diazepam. Rats, n=7 per group, were divided into 3 dose-dependent treatment groups (highest, middle, and lowest). Each rat within a treatment group received a single dose of diazepam, lorazepam, zolpidem and vehicle. All three drugs induced dose-dependent decreases in body temperature, locomotor activity and electromyographic (EMG) activity. Administration of zolpidem (5 and 10 mg/kg) resulted in maximal decrements in locomotor activity that were comparable to those elicited by both diazepam (10 and 20 mg/kg) and lorazepam (12.5 and 25 mg/kg). Zolpidem (10 mg/kg) decreased EMG activity levels to approximately 45% of vehicle treated controls; a value similar to that induced by diazepam (2.5 mg/kg). These data suggest that the imidazopyridine zolpidem has a similar profile of acute effects in comparison to the benzodiazepines diazepam and lorazepam. However, the relative magnitude of the effects differed, with zolpidem producing less hypothermia and muscle relaxation than the two benzodiazepines.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11311900&dopt=Abstract
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J Neurosci. 2001 May 1;21(9):3009-16.
GABA(A) receptor alpha1 subunit deletion prevents developmental changes of inhibitory synaptic currents in cerebellar neurons.
Vicini S, Ferguson C, Prybylowski K, Kralic J, Morrow AL, Homanics GE.
Department of Physiology and Biophysics, Georgetown University Medical School, Washington, DC 20007, USA. svicin01
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georgetown.edu
Developmental changes in miniature IPSC (mIPSC) kinetics have been demonstrated previously in cerebellar neurons in rodents. We report that these kinetic changes in mice are determined primarily by developmental changes in GABA(A) receptor subunit expression. mIPSCs were studied by whole-cell recordings in cerebellar slices, prepared from postnatal day 11 (P11) and P35 mice. Similar to reports in granule neurons, wild-type cerebellar stellate neuron mIPSCs at P11 had slow decay kinetics, whereas P35 mIPSCs decayed five times faster. When mIPSCs in cerebellar stellate neurons were compared between wild-type (+/+) and GABA(A) receptor alpha1 subunit-deficient (-/-) littermates at P35, we observed dramatically slower mIPSC decay rates in -/- animals. We took advantage of the greater potency of imidazopyridines for GABA current potentiation with alpha1 subunit-containing receptors to characterize the relative contribution of alpha1 subunits in native receptors on inhibitory synapses of cerebellar granule neurons. Zolpidem-induced prolongation of mIPSC decay was variable among distinct cells, but it increased during development in wild-type mice. Similarly, Zolpidem prolongation of mIPSC decay rate was significantly greater in adult +/+ mice than in knock-outs. We propose that an increased alpha1 subunit assembly in postsynaptic receptors of cerebellar inhibitory synapses is responsible for the fast inhibitory synaptic currents that are normally observed during postnatal development.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11312285&dopt=Abstract
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