Delving into the Latest Updates on Loxapine Succinate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Loxapine, Loxapine succinate (USP), 琥珀酸洛沙平

+ [7]

Target

5-HT receptor x DRDs

Mechanism

5-HT receptor antagonists(Serotonin (5-HT) receptor antagonists), DRDs antagonists(Dopamine receptors antagonists)

Therapeutic Areas

Other DiseasesNervous System DiseasesImmune System Diseases+ [1]

Active Indication-

Inactive Indication

AsthmaMigraine DisordersSchizophrenia

Originator Organization

Actavis A/S

Active Organization-

Inactive Organization

Alexza Pharmaceuticals, Inc.Teva Branded Pharmaceutical Products R&D, Inc.

Drug Highest PhaseApproved

First Approval Date

US (25 Feb 1975),

Schizophrenia

Regulation-

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Structure

Molecular FormulaC22H24ClN3O5

InChIKeyYQZBAXDVDZTKEQ-UHFFFAOYSA-N

CAS Registry27833-64-3

View All Structures (2)

BACKGROUND/AIMWe investigated drugs that could sensitize P-glycoprotein (P-gp)-overexpressing drug-resistant cancer cells to vincristine (VIC) or eribulin treatment and assessed their associated mechanisms of action.MATERIALS AND METHODSWe investigated 15 bipolar drugs (quetiapine, risperidone, clozapine, asenapine, iloperidone, paliperidone, ziprasidone, trifluoperazine, loxapine succinate, pilocarpine, valproic acid, carbamazepine, levetiracetam, topiramate, and felbamate) to identify drugs with a sensitizing effect on VIC-resistant KBV20C cells at relatively low doses. Fluorescence-activated cell sorting (FACS), annexin V analyses, and rhodamine uptake tests were performed to further investigate the mechanism of action.RESULTSWe found that co-treatment with half the tested drugs (quetiapine, iloperidone, trifluoperazine, loxapine, risperidone, ziprasidone, or felbamate) at low doses could highly sensitize VIC-resistant KBV20C cells. With lower amounts of the bipolar drugs or VIC, we found that among the 15 bipolar drugs tested, 2 combinations (VIC-quetiapine and VIC-trifluoperazine) had much higher sensitization effects, suggesting that lower effective doses were sufficient for sensitizing P-gp-overexpressing resistant cells compared to those required with the other drugs. Furthermore, when we compared quetiapine and trifluoperazine to previously known bipolar drugs (fluphenazine, thioridazine, pimozide, or aripiprazole), we found that aripiprazole, administered at lower doses, had a much higher sensitization effect. We also demonstrated that co-treatment with another anti-mitotic drug (eribulin) increased the sensitization of KBV20C cells similar to VIC. We also found that aripiprazole had higher P-gp-inhibitory activity than the other bipolar drugs, indicating that this activity was involved in the higher level of VIC-aripiprazole sensitization.CONCLUSIONCo-treatment of anti-mitotic drug-resistant cancer cells with a low dose of aripiprazole had the strongest sensitization effect and is highly dependent on P-gp-inhibitory activity.

01 Dec 2018·Journal of Pharmaceutical AnalysisQ2 · MEDICINE

Development and validation of an HPLC-UV method for analysis of methylphenidate hydrochloride and loxapine succinate in an activated carbon disposal system

Q2 · MEDICINE

ArticleOA

Author: Banga, Ajay K ; Fowler, William ; Bakshi, Pooja ; Korey, Andrew

Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration (FDA) recommends the proper disposal of unused prescribed medications to maintain safety and prevent environmental hazards. However, many of the current disposal techniques do not properly address safety. A drug disposal pouch containing granular activated carbon offers a unique disposal method to deactivate residual or expired medication in a convenient, effective, and safe manner. A robust and validated method for methylphenidate hydrochloride and loxapine succinate was developed using high-performance liquid chromatography (HPLC) and the deactivation efficiency of the disposal system was tested. Methylphenidate hydrochloride was analyzed on a C₁₈ analytical column (250 mm × 4.60 mm, 100Å) using acetonitrile-water (0.05% (v/v) trifluoroacetic acid) as the mobile phase at a flow rate of 1.0 mL/min with a run time of 15 min and retention time of 7.8 min. Loxapine succinate was separated on a C₈ 100Å (250 mm × 4.6 mm, 5 µm) column maintained at 25 °C using a flow rate of 1.0 mL/min. The run time was 10 min and the retention time of the drug was around 4.6 min. Mobile phase was composed of acetonitrile and water (0.3% triethylamine) at pH 3.0 as 40:60 (v/v). Reference standard solutions (100 µg/mL) for both drugs were prepared by dissolving in mobile phases. These methods provide good linearity (R ² = 0.999) over the range of 5-100 µg/mL for methylphenidate hydrochloride and 0.1-100 µg/mL for loxapine succinate. The assay methods were successfully applied to study the deactivation of these drugs.

01 Apr 2018·International Journal of NeuropsychopharmacologyQ2 · MEDICINE

The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?

Q2 · MEDICINE

ArticleOA

Author: Ouzid, Mehemed ; Llorca, Pierre-Michel ; Ferreri, Florian ; Drapier, Dominique ; Baloche, Emmanuelle ; Zimmer, Luc

BackgroundThe denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action.Materials and MethodsCompetition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145, and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate.ResultsIn cell cultures, the measured Kb confirmed high affinity of loxapine for the D2; intermediate affinity for the D1, D4, D5, 5-HT2C receptorsl and a lack of affinity toward D3, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors. In brain tissue, PET autoradiographies showed a radiopharmaceutical displacement at low concentrations of loxapine on D2 and 5-HT2A receptors.ConclusionThis preclinical study reveals that loxapine receptorial spectrum is close to an "atypical" profile (D2/5HT2A ratio, 1.14). Loxapine is rightly classified as a DS-RAn agent in the Neuroscience Based Nomenclature classification.

100 Deals associated with Loxapine Succinate

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