Tag: 575.6108

Involvement of 5-HT_2A receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats was written by Nakamura, Yuka;Kitamura, Yoshihisa;Sumiyoshi, Yusuke;Naito, Nanami;Kan, Shiho;Ushio, Soichiro;Miyazaki, Ikuko;Asanuma, Masato;Sendo, Toshiaki. And the article was included in Journal of Pharmacological Sciences (Amsterdam, Netherlands) in 2018.SDS of cas: 112457-95-1 This article mentions the following:

We examined whether combination treatment with doxorubicin and cyclophosphamide, a traditional chemotherapy for breast cancer, induced anxiety-like behavior in rats. Furthermore, we evaluated the role of the serotonin (5-HT)_2A receptor subtype in the anxiety-like behavior induced by such chemotherapy. Rats were i.p. injected with doxorubicin and cyclophosphamide once a week for 2 wk. This caused the rats to display anxiety-like behavior during the light-dark test. In addition, we examined the rats’ 5-HT_2A receptor-mediated behavioral responses. Combination treatment with doxorubicin and cyclophosphamide significantly increased (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, (a 5-HT_2A receptor agonist)-induced wet-dog shake activity. This anxiety-like behavior was significantly inhibited by mirtazapine, a 5-HT_2A receptor antagonist/5-HT_1A receptor agonist, and tandospirone, a partial 5-HT_1A receptor agonist, but not by fluoxetine, a selective serotonin reuptake inhibitor. The anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment is mediated by hyperfunctioning of the 5-HT_2A receptor. Thus, 5-HT_2A receptor antagonists or 5-HT_1A receptor agonists might be useful for treating chemotherapy-induced anxiety disorders. In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1SDS of cas: 112457-95-1).

rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).SDS of cas: 112457-95-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia. was written by Elkina, Yulia;Palus, Sandra;Tschirner, Anika;Hartmann, Kai;von Haehling, Stephan;Doehner, Wolfram;Mayer, Ulrike;Coats, Andrew J S;Beadle, John;Anker, Stefan D;Springer, Jochen. And the article was included in International journal of cardiology in 2013.HPLC of Formula: 112457-95-1 This article mentions the following:

BACKGROUND: Cancer cachexia is thought to be the cause of >20% of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia. METHODS: The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1mg/kg/d (LD), 10mg/kg/d (HD) tandospirone or placebo. Weight, body composition (NMR), cardiac function (echocardiography), activity and food intake were assessed. Noradrenalin and cortisol were measured in plasma and caspase activity in skeletal muscle. RESULTS: Ten mg/kg/d tandospirone decreased the loss of body weight (p=0.0003) compared to placebo animals, mainly due to preservation of muscle mass (p<0.001), while 1mg/kg/d tandospirone was not effective. Locomotor activity (p=0.0007) and food intake (p=0.0001) were increased by HD tandospirone. The weight (p=0.0277) and function of heart (left ventricular mass, fractional shortening, stroke volume, ejection fraction, all p<0.05) were significantly improved. In the HD tandospirone group, plasma levels of noradrenalin and cortisol were significantly reduced by 49% and 52%, respectively, which may have contributed to the lower caspase activity in the gastrocnemius muscle. Most importantly, HD tandospirone significantly improved survival compared to placebo rats (HR: 0.34; 95% CI: 0.13-0.86; p=0.0495). CONCLUSION: Tandospirone showed significant beneficial effects in the Yoshida hepatoma cancer cachexia model and should be further examined as a prospective drug for this syndrome. In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1HPLC of Formula: 112457-95-1).

rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.HPLC of Formula: 112457-95-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Combined serotonin (5-HT)_1A agonism, 5-HT_2A and dopamine D₂ receptor antagonism reproduces atypical antipsychotic drug effects on phencyclidine-impaired novel object recognition in rats was written by Oyamada, Yoshihiro;Horiguchi, Masakuni;Rajagopal, Lakshmi;Miyauchi, Masanori;Meltzer, Herbert Y.. And the article was included in Behavioural Brain Research in 2015.Electric Literature of C27H37N5O9 This article mentions the following:

Subchronic administration of an N-methyl-D-aspartate receptor (NMDAR) antagonist, e.g. phencyclidine (PCP), produces prolonged impairment of novel object recognition (NOR), suggesting they constitute a hypoglutamate-based model of cognitive impairment in schizophrenia (CIS). Acute administration of atypical, e.g. lurasidone, but not typical antipsychotic drugs (APDs), e.g. haloperidol, are able to restore NOR following PCP (acute reversal model). Furthermore, atypical APDs, when co-administered with PCP, have been shown to prevent development of NOR deficits (prevention model). Most atypical, but not typical APDs, are more potent 5-HT_2A receptor inverse agonists than dopamine (DA) D₂ antagonists, and have been shown to enhance cortical and hippocampal efflux and to be direct or indirect 5-HT_1A agonists in vivo. To further clarify the importance of these actions to the restoration of NOR by atypical APDs, sub-effective or non-EDs of combinations of the 5-HT_1A partial agonist (tandospirone), the 5-HT_2A inverse agonist (pimavanserin), or the D₂ antagonist (haloperidol), as well as the combination of all three agents, were studied in the acute reversal and prevention PCP models of CIS. Only the combination of all three agents restored NOR and prevented the development of PCP-induced deficit. Thus, this triple combination of 5-HT_1A agonism, 5-HT_2A antagonism/inverse agonism, and D₂ antagonism is able to mimic the ability of atypical APDs to prevent or ameliorate the PCP-induced NOR deficit, possibly by stimulating signaling cascades from D₁ and 5-HT_1A receptor stimulation, modulated by D₂ and 5-HT_2A receptor antagonism. In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1Electric Literature of C27H37N5O9).

rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Electric Literature of C27H37N5O9

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Inhibitory effects of antipsychotic and anxiolytic agents on stress-induced degranulation of mouse dermal mast cells. was written by Shimoda, T;Liang, Z;Suzuki, H;Kawana, S. And the article was included in Clinical and experimental dermatology in 2010.Formula: C27H37N5O9 This article mentions the following:

BACKGROUND: Various psychological stresses induce degranulation of mast cells. It has been confirmed by animal experiments that stress induced by restraint promotes mast-cell degranulation in various organs, and that the degranulation is inhibited by pretreatment with corticotropin-releasing factor (CRF)-neutralizing antibodies, CRF receptor antagonists, and neurotensin (NT) antagonists. Previous studies have suggested that anxiety and fear induced in animals by psychological stressors promote the production and release of various neuropeptides and neurotransmitters, and induce degranulation of mast cells in several organs. AIM: To evaluate the effect of prior treatment with antipsychotic and anxiolytic agents to inhibit foot-shock (FS) stress-induced degranulation of mouse dermal mast cells. METHODS: Using a communication box system, FS was administered to mice and the degranulated dermal mast cells were counted. Chlorpromazine (2 or 4 mg/kg body weight), tandospirone (10 mg/kg body weight) or CRA1000, a selective non-peptidic CRF receptor type 1 antagonist (10 or 100 mg/kg body weight) was injected intraperitoneally 1 h before exposure to FS. RESULTS: After FS was administered, the number of dermal mast cells did not change. However, FS significantly increased the proportion of degranulated mast cells. Pretreatment of mice with chlorpromazine hydrochloride, an antipsychotic agent (2 or 4 mg/kg), or the anxiolytic agents tandospirone citrate (10 mg/kg) or CRA1000 (10 or 100 mg/kg), significantly inhibited the FS-induced mast-cell degranulation (P < 0.05, P < 0.01, P < 0.05, P < 0.05, and P < 0.05, respectively). CONCLUSIONS: Antipsychotic and anxiolytic agents may be effective treatments for stress-aggravated inflammatory skin diseases by inhibition of mast-cell degranulation. In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1Formula: C27H37N5O9).

rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Formula: C27H37N5O9

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Simultaneous determination of tandospirone and its active metabolite, 1-[2-pyrimidyl]-piperazine in rat plasma by LC-MS/MS and its application to a pharmacokinetic study was written by Hu, Wenya;Jia, Mi;He, Siyan;Xie, Huiru;Jiang, Xuehua;Wang, Ling. And the article was included in Biomedical Chromatography in 2019.Category: piperazines This article mentions the following:

A rapid, sensitive and selective liquid chromatog.-tandem mass spectrometry method for the detection of tandospirone (TDS) and its active metabolite 1-[2-pyrimidyl]-piperazine (1-PP) in Sprague-Dawley rat plasma is described. It was employed in a pharmacokinetic study. These analytes and the internal standards were extracted from plasma using protein precipitation with acetonitrile, then separated on a CAPCELL PAK ADME C₁₈ column using a mobile phase of acetonitrile and 5 mM ammonium formate acidified with formic acid (0.1%, volume/volume) at a total flow rate of 0.4 mL/min. The detection was performed with a tandem mass spectrometer equipped with an electrospray ionization source. The method was validated to quantify the concentration ranges of 1.000-500.0 ng/mL for TDS and 10.00-500.0 ng/mL for 1-PP. Total time for each chromatograph was 3.0 min. The intra-day precision was between 1.42 and 6.69% and the accuracy ranged from 95.74 to 110.18% for all analytes. Inter-day precision and accuracy ranged from 2.47 to 6.02% and from 98.37 to 105.62%, resp. The lower limits of quantification were 1.000 ng/mL for TDS and 10.00 ng/mL for 1-PP. This method provided a fast, sensitive and selective anal. tool for quantification of tandospirone and its metabolite 1-PP in plasma necessary for the pharmacokinetic investigation. In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1Category: piperazines).

rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Category: piperazines

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

The effects of acute treatment with tandospirone, diazepam, and placebo on driving performance and cognitive function in healthy volunteers was written by Takahashi, Masahiro;Iwamoto, Kunihiro;Kawamura, Yukiko;Nakamura, Yukako;Ishihara, Ryoko;Uchiyama, Yuji;Ebe, Kazutoshi;Noda, Akiko;Noda, Yukihiro;Yoshida, Keizo;Iidaka, Tetsuya;Ozaki, Norio. And the article was included in Human Psychopharmacology in 2010.Category: piperazines This article mentions the following:

Objective: To assess the effects of two anxiolytics, diazepam and tandospirone, on driving performance from methodol. viewpoints taking frequent rear-end collisions into account. Methods: In this double-blinded, three-way crossover trial, 18 healthy males received acute doses of 20 mg tandospirone (TSP), 5 mg diazepam (DZP), and placebo (PCB). The subjects were administered three driving tasks-road tracking, car following, and harsha braking-performed using a driving simulator and three cognitive tasks-Wisconsin Card Sorting Test, Continuous Performance Test, and N-back test-at baseline and at 1 and 4 h post-dosing. The Stanford Sleepiness Scale scores were also assessed. Results: DZP nonsignificantly increased the percent change of brake reaction time (BRT) as compared to PCB at 4 h post-dosing. TSP nonsignificantly decreased the percent change of BRT as compared to PCB. Consequently, there was a significant difference in the percent change of BRT between DZP and TSP at 4 h post-dosing. For the remaining tasks, no statistically significant effects of treatment were observed Conclusions: Acute doses of DZP significantly impaired the harsh-braking performance as compared to acute doses of TSP. These findings suggest that TSP may be used more safely in patients’ driving activities. In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1Category: piperazines).

rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Category: piperazines

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Clinical evaluation of the efficacy and safety of tandospirone versus sertraline monotherapy for social anxiety disorder: a randomized open-label trial was written by Huang, Xiao;Li, Chao;Li, Wei-hui;Luo, Yan-li;Wang, Biao;Zhang, Wei;Gan, Jian-jun;Ji, Jian-lin. And the article was included in Human Psychopharmacology in 2013.Safety of rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate This article mentions the following:

Objective : Although selective serotonin reuptake inhibitors are now established as first-line pharmacotherapy for social anxiety disorder (SAD), other agents with different mechanisms have shown promise in treating SAD. The aim of this study was to examine the efficacy and safety of tandospirone in treating adolescents with SAD. Methods : Adolescent patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for SAD were randomly assigned (1:1) to open-label treatment with either tandospirone or sertraline for 8 wk. The primary outcome measures were changes from baseline in the Hamilton Anxiety (HAM-A) scale and response using the Clin. Global Impression of Improvement (CGI-I) scale. Results : The adjusted mean change in HAM-A scores from baseline was indicating a significant improvement over baseline in both treatment arms (p < 0.0001). The mean CGI-I scale score at week was with no significant difference between the two arms (p = 0.42). Rates of response were 48.6% for tandospirone and 55.6% for sertraline using the CGI-I. Response rates were 37.1% for tandospirone and 41.7% for sertraline using a HAM-A response criterion (≥50% reduction). The adjusted mean change in Social Phobia Inventory scores from baseline was indicating a significant improvement over baseline in both treatment arms (p < 0.0001). Conclusions : Tandospirone is safe and effective and appears non-inferior to sertraline for SAD in youths. Copyright © 2013 John Wiley & Sons, Ltd. In the experiment, the researchers used many compounds, for example, rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1Safety of rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate).

rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate (cas: 112457-95-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Safety of rel-(3aR,4S,7R,7aS)-2-(4-(4-(Pyrimidin-2-yl)piperazin-1-yl)butyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 2-hydroxypropane-1,2,3-tricarboxylate

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics