Hypnotics and Sedatives

Skinner, Brian W.; Curtis, K. Alexandra; Goodhart, Angela L.

doi:10.1016/bs.seda.2018.06.002

Cited by 2 publications

(1 citation statement)

References 36 publications

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“…In one of the stages of the inflammatory process, prostaglandins, also called eicosanoids, are synthesized by triggering various stimuli that activate cell membrane receptors, when coupled with a regulatory protein that results in the activation of phospholipase A2 or with an increase in the concentration of Ca +2 . This type of enzyme hydrolyzes membrane phospholipids, consequently releasing the cascade of arachidonic acid, which is a substrate for the synthesis of physiopatological and inductive prostaglandins; see Figure 1 below [3]. Prostaglandins-endoperoxide synthase (PTGS) are known as cyclooxygenases responsible for the synthesis of prostaglandins that are percussive biologically active molecules.…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches

et al. 2020

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Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase-2 (COX-2) that were developed in order to avoid the side effects of non-selective inhibitors of COX-1. Thus, the present study aims to identify new selective chemical entities for the COX-2 enzyme via molecular modeling approaches. The best pharmacophore model was used to identify compounds within the ZINC database. The molecular properties were determined and selected with Pearson’s correlation for the construction of quantitative structure–activity relationship (QSAR) models to predict the biological activities of the compounds obtained with virtual screening. The pharmacokinetic/toxicological profiles of the compounds were determined, as well as the binding modes through molecular docking compared to commercial compounds (rofecoxib and celecoxib). The QSAR analysis showed a fit with R = 0.9617, R2 = 0.9250, standard error of estimate (SEE) = 0.2238, and F = 46.2739, with the tetra-parametric regression model. After the analysis, only three promising inhibitors were selected, Z-964, Z-627, and Z-814, with their predicted pIC50 (−log IC50) values, Z-814 = 7.9484, Z-627 = 9.3458, and Z-964 = 9.5272. All candidates inhibitors complied with Lipinski’s rule of five, which predicts a good oral availability and can be used in in vitro and in vivo tests in the zebrafish model in order to confirm the obtained in silico data.

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Section: Introductionmentioning

confidence: 99%

Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches

et al. 2020

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Adrenergic receptors gene polymorphisms and autonomic nervous control of heart and vascular tone

Matušková¹,

Javorka²

2022

Physiol Res

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Adrenergic receptors (ARs) are the primary targets of catecholamines released from the sympathetic nerve endings during their activation. ARs play a central role in autonomic nervous system and serve as important targets of widely used drugs. Several ARs gene polymorphisms were found to be associated with cardiovascular disease in previous clinical studies. Although more precise mechanism of the polymorphisms influence on autonomic control of cardiovascular system was studied in many previous physiological studies, their results are not unequivocal. This paper reviews the results of clinical and physiological studies focused on the impact of selected common single nucleotide polymorphisms of ARs genes involved in sympathetic control on cardiovascular system and its control. In summary, many studies assessed only a very limited range of cardiovascular control related parameters providing only very limited view on the complex cardiovascular control. The overview of partially contradicting results underlines a need to examine wider range of cardiovascular measures including their reactivity under various stress conditions requiring further study. It is expected that an effect of one given polymorphism is not very prominent, but it is suggested that even subtle differences in cardiovascular control could – on a longer time scale – lead to the development of severe pathological consequences.

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Hypnotics and Sedatives

Cited by 2 publications

References 36 publications

Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches

Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches

Adrenergic receptors gene polymorphisms and autonomic nervous control of heart and vascular tone

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