China
Africa
Explore chapters and articles related to this topic
Benzodiazepines as anxiolytics
Published in Adam Doble, Ian L Martin, David Nutt, Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
Adam Doble, Ian L Martin, David Nutt
Finally, the possibility of an endogenous ligand or endozepine needs to be considered (the concept and evidence for such compounds is given later in this chapter). Such a substance would reduce the binding of the flumazenil tracer to the receptor and provide the picture described. However, this substance could not be an inverse agonist causing panic as flumazenil would have blocked it and so been anxiolytic not anxiogenic. However, it is possible that an endogenous agonist exists, possibly as a compensatory mechanism, and the anxiogenic effects of flumazenil are due to its displacing this from the receptor so precipitating a type of withdrawal anxiety. If an endogenous agonist exists, it can only be present in panic patients (and possibly GAD) as the controls did not get anxious.
Benzodiazepines, Benzodiazepine Receptors, and Endogenous Ligands
Published in Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen, Handbook of Depression and Anxiety, 2003
Over the years, several endogenous ligands [48] acting at the benzodiazepine binding site of GABAA receptors (endozepines) have been discovered, although a possible physiological function of none of these compounds so far has been definitely established. Thus, the purines inosine and hypoxanthine inhibit diazepam binding with IC50 values 400 to 1300 μM and 700 to 3700 |xM, respectively [49]. Similarly, adenosine [50] and S- adenosylhomocysteine [51] can inhibit benzodiazepine binding. Concentrations needed for these effects, however, seem to be high compared to the endogenous concentrations of these compounds [52].
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
Purdy, R. et al., Stress-induced elevations of γ-aminobutyric acid type A receptoractive steroids in the rat brain, Proc. Natl. Acad. Sci. U.S.A., 88, 4553, 1991. Papaioannou, A. et al., Sex differences in the effects of neonatal handling on the animal’s response to stress and the vulnerability for depressive behaviour, Behav. Brain Res., 129, 131, 2002.Patchev, V.K. et al., The neurosteroid tetrahydroprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in the rat hypothalamus, Neuropsychopharmacology, 15, 533, 1996.Mensah-Nyagan, A.G. et al., Regulation of neurosteroid biosynthesis in the frog diencephalon by GABA and endozepines, Horm. Behav., 40, 218, 2001.Schlinger, B.A., Soma, K.K., and London, S.E., Neurosteroids and brain sexual differentiation, Trends Neurosci., 24, 429, 2001.Kellogg, C.K. and Frye, C.A., Endogenous levels of 5α-reduced progestins and androgens in fetal vs. adult rat brains, Brain Res. Dev. Brain Res., 115, 17, 1999.Kehoe, P. et al., Central allopregnanolone is increased in rat pups in response to repeated, short episodes of neonatal isolation, Brain Res. Dev. Brain Res., 124,
The Possible Role of Endozepines in Sleep Regulation and Biomarker of Process S of the Borbély Sleep Model
Published in Chronobiology International, 2021
Simona Sher, Amit Green, Soliman Khatib, Yaron Dagan
The Two-Process Model of Sleep Regulation has been used for research and as a clinical approach for years. The model describes the integration of the circadian rhythm of arousal, Process C, and the homeostatic pressure to sleep, Process S. To the best of our knowledge, there is no known biological compound that explains Process S as melatonin and core body temperature (CBT) explains Process C. The only known measurement for Process S is the EEG and compared to the convenience of blood samples it is not an easy marker to measure. Furthermore, while Process S is known to be affected by sleep deprivation as the sleep pressure increases, Process C in contrast does not increase or decrease, although its phasing can be shifted with alteration in the sleep/wake routine (Borbély 1982; Daan et al. 1984). Endozepines are endogenous compounds that act like benzodiazepines, i.e., serving as ligands for the BZ binding sites on GABAA receptors. This binding to GABAAR leads to sedative and sleep-inducing effects, thus BZs are used as common anxiety and insomnia drugs (Farzampour et al. 2015; Tonon et al. 2020).
Anxiolytics targeting GABAA receptors: Insights on etifoxine
Published in The World Journal of Biological Psychiatry, 2018
Pierrick Poisbeau, Geraldine Gazzo, Laurent Calvel
A diversity of endogenous compounds, including endozepines, can modulate GABAAR activity. Endozepines bind to the benzodiazepine site of GABAAR, as demonstrated by their ability to displace diazepam from its binding site (Costa and Guidotti 1991). DBI (diazepam binding inhibitor, recently renamed ACBD1-acyl-coenzyme A binding domain containing 1 protein (Fan et al. 2010)) and its two major bioactive cleavage products, TTN (triakontatetraneuropeptide) and ODN (octadecaneuropeptide), are the main endozepines. Their physiological role is controversial, with the majority of research suggesting that endozepines are negative allosteric modulators (Guidotti et al. 1983; Bormann 1991), but some authors have accumulated evidence implying otherwise (Christian et al. 2013). Although little is known about endozepines, astrocytes seem to play a major role in the release of DBI and its conversion into active peptides (Loomis et al. 2010). Endozepines also bind to a mitochondrial translocator protein (TSPO), formerly known as the peripheral benzodiazepine receptor, which will be detailed more thoroughly later in this review.