Tag: 433.5658

Brexpiprazole Pharmacokinetics in CYP2D6 Poor Metabolizers: Using Physiologically Based Pharmacokinetic Modeling to Optimize Time to Effective Concentrations was written by Elmokadem, Ahmed;Bruno, Christopher D.;Housand, Conrad;Jordie, Eric Burroughs;Chow, Christina R.;Lesko, Lawrence J.;Greenblatt, David J.. And the article was included in Journal of Clinical Pharmacology in 2022.Category: piperazines This article mentions the following:

Brexpiprazole is an oral antipsychotic agent indicated for use in patients with schizophrenia, or as adjunctive treatment for major depressive disorder. As cytochrome P 450 (CYP) 2D6 contributes significantly to brexpiprazole metabolism, there is a label-recommended 50% reduction in dose among patients with the CYP2D6 poor metabolizer phenotype. This study uses a whole-body physiol. based pharmacokinetic (PBPK) model to compare the pharmacokinetics of brexpiprazole in patients known to be extensive metabolizers (EMs) and poor metabolizers (PMs). A PBPK model was constructed, verified, and validated against brexpiprazole clin. data, and simulations of 500 subjects were performed to establish the median time to effective concentrations in EMs and PMs. The PBPK simulations captured brexpiprazole PK well and demonstrated significant differences in the time to effective concentrations between EMs and PMs according to the label-recommended titration Addnl., these simulations suggest that CYP2D6 PMs consistently achieve lower min. concentrations during the dosing interval than CYP2D6 EMs. Simulations using an alternative dosing strategy of twice-daily dosing (as opposed to once daily) in PMs during the first week of brexpiprazole dosing yielded more consistent plasma concentrations between EMs and PMs, without exceeding the area under the plasma concentration-time curve observed in the EMs. Taken together, the results of these PBPK simulations suggest that product labeling for brexpiprazole titration in CYP2D6 PMs likely overcompensates for the decreased clearance seen in this population. We propose an alternative dosing strategy that decreases the time to effective concentrations and recommend a reevaluation of steady-state PK in this population to potentially allow for higher daily doses in CYP2D6 PMs. In the experiment, the researchers used many compounds, for example, 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9Category: piperazines).

7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9) 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

Copulatory Dyskinesia: Pathognomonic Manifestation of Tardive Dyskinesia. was written by Sharma, Vibhash D;Gupta, Harsh V;Espay, Alberto J. And the article was included in Tremor and other hyperkinetic movements (New York, N.Y.) in 2020.Synthetic Route of C25H27N3O2S This article mentions the following:

Background: Copulatory or pelvic thrusting dyskinesia is a subtype of tardive dyskinesia (TD) which is caused by exposure to dopamine blocking agents. Phenomenology shown: A man exhibiting rhythmic, stereotypical pelvic thrusting movements. Educational value: Recognition of copulatory dyskinesia as a distinctive iatrogenic disorder helps prevent unnecessary investigations and guides the implementation of corrective strategies. In the experiment, the researchers used many compounds, for example, 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9Synthetic Route of C25H27N3O2S).

7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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.Synthetic Route of C25H27N3O2S

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

Impulse control disorders by dopamine partial agonists: a pharmacovigilance-pharmacodynamic assessment through the FDA adverse event reporting system was written by Fusaroli, Michele;Raschi, Emanuel;Giunchi, Valentina;Menchetti, Marco;Giorgini, Roberto Rimondini;De Ponti, Fabrizio;Poluzzi, Elisabetta. And the article was included in International Journal of Neuropsychopharmacology in 2022.Product Details of 913611-97-9 This article mentions the following:

Background: The dopaminergic partial agonism of the so-called third-generation antipsychotics (TGAs; aripiprazole, brexpiprazole, cariprazine) is hypothesized to cause impulse control disorders (ICDs). Relevant warnings by the Food and Drug Administration (FDA) were posted on aripiprazole (2016) and brexpiprazole (2018). Our study investigated the FDA Adverse Event Reporting System and the pharmacodynamic CHEMBL database to further characterize TGA-induced ICDs. Methods: We downloaded and pre-processed the FDA Adverse Event Reporting System up to Dec. 2020. We adapted Bradford Hill criteria to assess each TGA’s -and secondarily other antipsychotics’-causal role in inducing ICDs (pathol. gambling, compulsive shopping, hyperphagia, hypersexuality), accounting for literature and disproportionality. ICD clin. features were analyzed, and their pathogenesis was investigated using receptor affinities. Results: A total of 2708 reports of TGA-related ICDs were found, primarily recording aripiprazole (2545 reports, 94%) among the drugs, and gambling (2018 reports, 75%) among the events. Bradford-Hill criteria displayed evidence for a causal role of each TGA consistent across subpopulations and when correcting for biases. Significant disproportionalities also emerged for lurasidone with compulsive shopping, hyperphagia, and hypersexuality, and olanzapine and ziprasidone with hyperphagia. Time to onset varied between days and years, and pos. dechallenge was observed in 20% of cases. Frequently, co-reported events were economic (50%), obsessive-compulsive (44%), and emotional conditions (34%). 5-Hydroxytryptamine receptor type 1a agonism emerged as an addnl. plausible pathogenetic mechanism. Conclusions: We detected an association between TGAs and ICDs and identified a new signal for lurasidone. ICD characteristics are behavior specific and may heavily impact on life. The role of 5-Hydroxytryptamine receptor type 1a agonism should be further explored. In the experiment, the researchers used many compounds, for example, 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9Product Details of 913611-97-9).

7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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.Product Details of 913611-97-9

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

Inhibitory effects of antipsychotics on the contractile response to acetylcholine in rat urinary bladder smooth muscles was written by Obara, Keisuke;Matsuoka, Yuka;Iwata, Naoya;Abe, Yukako;Ikegami, Yohei;Shioda, Nanako;Hattori, Yume;Hamamatsu, Shoko;Yoshioka, Kento;Yamaki, Fumiko;Matsuo, Kazuhiro;Yoshio, Takashi;Tanaka, Yoshio. And the article was included in Biological & Pharmaceutical Bulletin in 2021.Name: 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one This article mentions the following:

The clin. applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychol. symptoms, in patients with Alzheimer’s disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clin. available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clin. significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clin. achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10-5 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders. In the experiment, the researchers used many compounds, for example, 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9Name: 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one).

7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (cas: 913611-97-9) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Name: 7-(4-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one

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