Effects of 1,3,4-thiadiazine compound with antidepressant properties in ligation model of acute pancreatitis

Sarapultsev, Alexey; Чупахин, О. Н.; Rantsev, Maxim; Sarapultsev, Petr; Данилова, И. Г.; Medvedeva, S. Yu.; Sidorova, L. P.; Цейтлер, Т. А.; Бриллиант, С. А.; Tseĭlikman, Vadim

doi:10.4149/gpb_2018012

Cited by 4 publications

(4 citation statements)

References 49 publications

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“…В ходе проведенных нами параллельных исследований [32][33][34] установлено, что на молекулярном уровне действие соединения L-17 может быть обусловлено ингибированием действия переносчика серотонина (англ. Serotonin Transporter, SERT) и частичным антагонизмом к 5-HT 3 -и 5-HT 1A -рецепторам серотонина, что обусловливает анистрессорный эффект и проявляется повышением иммунореактивности c-Fos в миндалевидном теле и снижением ее в гиппокампе.…”

Section: Discussionunclassified

Correction of the Inflammatory Reaction in the Discrete Model of Acute Post-manipulation Pancreatitis

Rantsev,

Sarapultsev,

Chupakhin

2024

Урал. мед. журнал

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Introduction. Acute post-manipulation pancreatitis (APP) is a common complication of endoscopic interventions on the major duodenal papilla of the duodenum. Moderate acute pancreatitis develops more often than severe acute pancreatitis.The purpose of the work is to determine the effect of compound L-17 of the group of substituted thiadiazines on the severity of the inflammatory reaction in moderate severity APP.Materials and methods. The severity of the inflammatory reaction in experimental APP after surgery in rats using the compound L-17 was studied. During this study, laboratory indicators of the severity of the inflammatory reaction were assessed, including the leukocyte count and the level of increase in the concentration of the major interleukins. Furthermore, morphological data was analyzed to allow an assessment of the dynamics of the cellular composition of the inflammatory infiltrate of the pancreas in the APP in the experiment.Results. A decrease in the severity of the inflammatory reaction was shown according to leukocyte count, cytokine concentration, and a morphological study of the inflammatory infiltrate of the pancreas.Discussion. The effectiveness of the proposed surgical technique for the formation of APP has been proven by the development of acute pancreatitis in all animals operated. Most experimental methods for acute pancreatitis have no such effectiveness. The data obtained confirm the opinion of numerous authors that interventions on the major duodenal papilla are a risk factor for the development of APP. The study used the compound L-17, which is a representative of a new group of organic compounds, substituted thiadiazines, which have a disaggregant and anticoagulant effect. The effect of compound L-17 on the hemocoagulation parameters of blood is associated with the anti-inflammatory mechanism of action of compound L-17.Conclusion. Administration of compound L-17 in moderate-severity experimental APP can reduce the severity of the inflammatory reaction.

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Section: Discussionunclassified

Correction of the Inflammatory Reaction in the Discrete Model of Acute Post-manipulation Pancreatitis

Rantsev,

Sarapultsev,

Chupakhin

2024

Урал. мед. журнал

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“…In our previous studies, L-17 showed a putative therapeutic effect in animal models of myocardial infarction (MI) [2,3] and pancreatitis [4]. L-17 was also reported to attenuate the immune system response to the immobilization stress in rats, suggesting an immunostimulatory effect of this compound during the stress copying [5].…”

Section: Introductionmentioning

confidence: 97%

In Silico and In Vivo Assessment of L-17, a Thiadiazine Derivative with Putative Serotonin Reuptake Properties

Sarapultsev¹,

Grinchii²,

Paliokha³

et al. 2021

Preprint

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L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

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“…L-17 (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide; Fig. 1) is a thiadiazine derivative, synthesized by cyclocondensation of α-bromoacetophenone with the original morpholine-4-carbothionic acid hydrazide [1]: In our previous studies, L-17 we have shown a putative therapeutic effect of myocardial infarction (MI) [2][3][4] and pancreatitis [5] in animal models. L-17 has also been reported to attenuate the immune system response to the immobilization stress in rats, suggesting an immunostimulatory effect of this compound during the stress copying [4].…”

Section: Introductionmentioning

confidence: 99%

Combined in silico, ex vivo, and in vivo Assessment of L-17, a Thiadiazine Derivative With Putative Neuroprotective and Antidepressant-Like Effects

Sarapultsev¹,

Vassiliev²,

Grinchii³

et al. 2021

Preprint

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L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico, ex vivo, and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) receptors are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. Acute pre-treatment with L-17 robustly increased c-Fos immunoreactivity in the amygdala (central nucleus), suggesting increased neuronal excitability in this brain area after L-17 administration. Acute L-17 also dose-dependently inhibited of 5-HT neurons of the dorsal raphe nucleus (DRN). This inhibition was partially reversed by subsequent administration of WAY100135, suggesting the involvement of extracellular 5-HT. Based on in silico predictions, c-Fos immunohistochemistry, and in vivo electrophysiology, we suggest that L-17 is a potent 5-HT reuptake inhibitor and/or partial 5-HT1A receptor antagonist. Thus, L-17 might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardio-protective properties, it can be useful in post-stroke and post-myocardial infarction (MI) depression. In general, combined in silico predictions and ex vivo neurochemical and in vivo electrophysiological assessment might be a useful strategy for early preclinical assessment of the affectivity and neural mechanism in action of the novel CNS drugs.

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Effects of 1,3,4-thiadiazine compound with antidepressant properties in ligation model of acute pancreatitis

Cited by 4 publications

References 49 publications

Correction of the Inflammatory Reaction in the Discrete Model of Acute Post-manipulation Pancreatitis

Correction of the Inflammatory Reaction in the Discrete Model of Acute Post-manipulation Pancreatitis

In Silico and In Vivo Assessment of L-17, a Thiadiazine Derivative with Putative Serotonin Reuptake Properties

Combined <em>in silico,</em> <em>ex vivo</em>, and <em>in vivo</em> Assessment of L-17, a Thiadiazine Derivative With Putative Neuroprotective and Antidepressant-Like Effects

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