The impact of immunomodulator compound from the group of substituted thiadiazines on the course of stress reaction

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

“…This was confirmed by stress immobilization experiments where the substituted 1,3,4-thiadiazine L-17 lowered reac-tion to stress (Sarapultsev et al 2015) and by the results of pharmacological evaluation (Sarapultsev et al 2016). A report demonstrated that L-17 combined adrenergic, cholinergic and serotonin blockers and exerted its best effect in a similar concentration range to that used for the atypical antipsychotic agent Eglonyl (sulpiride) for antidepressants such as amitriptyline and in the alpha-blocker pyrroxanum (Sarapultsev et al 2016).…”

“…The proven ability of thiadiazine compounds such as L-17 to increase resistance to stress (Sarapultsev et al 2015) explains the observed decrease in neutrophilia and neutrophil count in inflammatory foci and the revealed inhibition of SI.…”

“…2-morpholino-5-phenyl-6H-1,3,4-thiadiazine hydrobromide (compound L-17) (Reaxys RN=14755889, CAS NUMBER 193208-23-0) from the group of substituted 1,3,4-thiadiazines studied in these experiments has proven a biological effect (Rantsev et al 2013;Sarapultsev et al 2014Sarapultsev et al , 2015Sarapultsev et al , 2016. The lethal dose of L-17 (LD50) is 434 mg/ kg (by weight), and the compound is a registered invention (United States Patent No 6313111 of 6 November 2001, PCT RF Patent No 2259371 of 27 August 2005.…”

“…These mechanisms were mediated by the reduction of proinflammatory and anti-inflammatory interleukin levels by L-17. However, increased interleukins and neutrophilia depend on the severity of stress in tissue damage; hence, it is assumed that the major action mechanism of L-17 is anti-stress activity as previously described in the stress immobilization model (Sarapultsev et al 2015).…”

“…The ability of substituted 1,3,4-thiadiazine compounds to lower stress reaction was previously described (Sarapultsev et al 2015), and their ability to act on both serotonin and adrenergic systems has been proposed (Sarapultsev et al 2016).. Here, a singular synchronized-action on serotonergic and adrenergic systems, also seen in psychotropic drugs, significantly enhanced their therapeutic effect (Arnsten 2004) because alpha-1 and serotonin (5HT2A) receptors are involved in the common phosphatidyl inositol/protein kinase C intracellular pathway via Gq proteins (Duman and Nestler 1995).…”