Zaleplon [BSA]

Purpose: Although different forms of pharmacological intervention are often prescribed for insomnia disorder, the comparative efficacies among various drugs remain unclear. We therefore conducted this study to quantitatively compare the efficacy of various pharmacotherapies for insomnia by modeling. Methods: We searched PubMed, EMBASE and Cochrane Library databases for randomized placebo-controlled trials of insomnia medications that were conducted within a designated time period (from the inception dates to May 16, 2019). Pharmacodynamic models were established to describe the time course of changes from baseline in selected sleep parameters. Sleep quality and dropout rates were also compared by a single-arm meta-analysis. Results: In sum, 43 studies covering 44 trials (14,535 patients) were included in the analysis. The drugs evaluated included flurazepam, quazepam, temazepam, triazolam, eszopiclone, zaleplon, zolpidem, extended-release zolpidem, suvorexant, ramelteon and doxepin. The established models revealed eszopiclone had the highest efficacy in terms of sleep latency (SL), total sleep time (TST), and sleep quality, and was also associated with the lowest dropout rates. The effect of suvorexant on the parameter 'wake after sleep onset' (WASO) was significantly higher than that of the other drugs analyzed. Conclusions: Each drug has its own characteristics in the treatment of insomnia, and this needs to be taken into consideration to meet individual clinical needs. These results serve as a quantitative supplement for clinical practice by reflecting the difference in efficacy of various drugs in the treatment of insomnia. (C) 2020 Elsevier B.V. All rights reserved.

In vitro studies show that the abused inhalant toluene affects a number of ligand-gated ion channels. The two most consistently implicated of these are gamma-aminobutyric acid type A (GABA(A)) receptors which are positively modulated by toluene and N-methyl-D-aspartate (NMDA) receptors which are negatively modulated by toluene. Behavioral studies also suggest an interaction of toluene with GABA(A) and/or NMDA receptors but it is unclear if these receptors underlie the abuse-related intoxicating effects of toluene. Seventeen B6SJLF1/J mice were trained using a two-choice operant drug discrimination procedure to discriminate 10 min of exposure to 2000 ppm toluene vapor from 10 min of exposure to air The discrimination was acquired in a mean of 65 training sessions. The stimulus effects of 2000 ppm toluene vapor were exposure concentration-dependent but rapidly diminished following the cessation of vapor exposure. The stimulus effects of toluene generalized to the chlorinated hydrocarbon vapor perchlorethylene but not 1,1,2-trichloroethane nor the volatile anesthetic isoflurane. The competitive NMDA antagonist CGS-19755, the uncompetitive antagonist dizocilpine and the glycine-site antagonist L701,324 all failed to substitute for toluene. The classical nonselective benzodiazepines midazolam and chlordiazepoxide produced toluene-like stimulus effects but the alpha 1 subunit preferring positive GABA(A) modulator zaleplon failed to substitute for toluene. The barbiturates pentobarbital and methohexital and the GABA(A)-positive modulator neurosteroid allopregnanolone did not substitute for toluene. These data suggest that the stimulus effects of toluene may be at least partially mediated by benzodiazepine-like positive allosteric modulation of GABA(A) receptors containing alpha 2, 3 or 5 subunits. (C) 2013 Elsevier B.V. All rights reserved