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Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
Recent studies104,105 have examined the effects of benzodiazepines on the activities of the various 3a HSDs (ARK1C1-4) (Table 1.3). In general, several benzodiazepines inhibit the 3a HSD isoforms to varying extents and have IC50 values in the micromolar range. Type IV (20a HSD) and type III differ by seven amino acids,102,240 and several benzodiazepines inhibited these enzymes similarly. Two exceptions were medazepam and nitrazepam, in which the IC50 for type IV was three- to fourfold lower than that for type III. The data suggest that these benzodiazepines would be beneficial for inhibiting 20a HSD activity, and hence inhibiting the conversion of potent neuroactive steroids to less potent neurosteroids. Inhibition of type I (liver) and type II by benzodiazepines was different than the inhibition of the type III and IV enzymes; in general, the benzodiazepines had higher IC50s for the type I and II enzymes, and type II was specifically potently inhibited by cloxazolam. Since the type II enzyme uses DHT, and not 5α DHβ or 5α DH-DOC, as substrate, these data would suggest that cloxazolam would inhibit the synthesis of the neurosteroid androstanediol, but not the synthesis of allopregnanolone or 3a5α TH-DOC.
Risks and benefits of medications for panic disorder: a comparison of SSRIs and benzodiazepines
Published in Expert Opinion on Drug Safety, 2018
Laiana A. Quagliato, Rafael C. Freire, Antonio E. Nardi
The authors used the following selection criteria for articles in this review. First, the article had to report on an empirical study in which the pharmacological treatment was applied to a sample of adult subjects diagnosed with PD with or without agoraphobia based on diagnostic criteria recognized by the scientific community. Second, the study had to be an open or placebo-controlled clinical trial. Articles published in English were searched in Medline, PubMed and Web of Science databases, using the following search words: (1). PD or panic attacks and (2). SSRI or citalopram or escitalopram or paroxetine or fluoxetine or fluvoxamine or sertraline, and (3). Benzodiazepines or clonazepam or alprazolam or lorazepam or bromazepam or clobazam or cloxazolam or diazepam. The time period for the literature search was 1997–2017. Articles were excluded if they involved any modality of psychotherapy, medications other than SSRIs and benzodiazepines, studies with no placebo group, and/or included individuals with clinical or psychiatric comorbidities associated with PD. Also, studies with fewer than 10 patients and articles on augmentation treatment or other non-pharmacological treatments such as transcranial magnetic stimulation were excluded. Meeting abstracts, congress proceedings, case reports, reviews, book reviews, corrections, editorials, news items, and reprints were excluded. References cited in the selected papers were also searched manually to ensure that no relevant study on this topic was left out.