Loxapine

CAS# 1977-10-2

Loxapine

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Chemical structure

Loxapine

3D structure

Chemical Properties of Loxapine

Cas No. 1977-10-2 SDF Download SDF
PubChem ID 3964 Appearance Powder
Formula C18H18ClN3O M.Wt 327.81
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : ≥ 33.33 mg/mL (101.67 mM)
*"≥" means soluble, but saturation unknown.
Chemical Name 8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzoxazepine
SMILES CN1CCN(CC1)C2=NC3=CC=CC=C3OC4=C2C=C(C=C4)Cl
Standard InChIKey XJGVXQDUIWGIRW-UHFFFAOYSA-N
Standard InChI InChI=1S/C18H18ClN3O/c1-21-8-10-22(11-9-21)18-14-12-13(19)6-7-16(14)23-17-5-3-2-4-15(17)20-18/h2-7,12H,8-11H2,1H3
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Loxapine Dilution Calculator

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Loxapine Molarity Calculator

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Preparing Stock Solutions of Loxapine

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.0505 mL 15.2527 mL 30.5055 mL 61.011 mL 76.2637 mL
5 mM 0.6101 mL 3.0505 mL 6.1011 mL 12.2022 mL 15.2527 mL
10 mM 0.3051 mL 1.5253 mL 3.0505 mL 6.1011 mL 7.6264 mL
50 mM 0.061 mL 0.3051 mL 0.6101 mL 1.2202 mL 1.5253 mL
100 mM 0.0305 mL 0.1525 mL 0.3051 mL 0.6101 mL 0.7626 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on Loxapine

Loxapine Succinate is a D2DR and D4DR inhibitor, serotonergic receptor antagonist and also a dibenzoxazepine anti-psychotic agent.

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References on Loxapine

Clinical Trial Simulations and Pharmacometric Analysis in Pediatrics: Application to Inhaled Loxapine in Children and Adolescents.[Pubmed:28205038]

Clin Pharmacokinet. 2017 Oct;56(10):1207-1217.

BACKGROUND AND OBJECTIVES: Loxapine for inhalation is a drug-device combination product approved in adults for the acute treatment of agitation associated with schizophrenia or bipolar I disorder. The primary objective of this study was to develop a clinical trial protocol to support a phase I pharmacokinetic study in children aged 10 years and older. In addition, this report details the results of the clinical study in relation to the predicted likelihood of achieving the target exposure associated with therapeutic effect in adults. METHODS: A nonlinear mixed-effects population pharmacokinetic model was developed using adult data and was adjusted for the targeted pediatric age groups by applying allometric scaling to account for body size effects. Based on this pediatric model, age-appropriate regimens to achieve Loxapine exposures similar to the ones associated with therapeutic effect in the adult studies were identified via trial simulation. D-optimal design and power analysis were conducted to identify optimal pharmacokinetic sampling times and sample size, respectively. RESULTS: The developed clinical trial design formed the basis of a phase I study to assess the safety and pharmacokinetics of Loxapine for inhalation in children aged 10 years and older (ClinicalTrials.gov ID: NCT02184767). CONCLUSION: The results of the study indicated that overall Loxapine exposures were consistent with what had been predicted by the trial simulations. The presented approach illustrates how modeling and simulation can assist in the design of informative clinical trials to identify safe and effective doses and dose ranges in children and adolescents.

Dopamine antagonists for treatment resistance in autism spectrum disorders: review and focus on BDNF stimulators loxapine and amitriptyline.[Pubmed:28335658]

Expert Opin Pharmacother. 2017 Apr;18(6):581-588.

INTRODUCTION: Drug development and repurposing are urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. Areas covered: We review dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD. The older antipsychotic Loxapine is discussed in terms of preliminary albeit limited evidence in ASD. Emerging promise of amitriptyline in ASD is discussed, together with promising BDNF effects of Loxapine and amitriptyline. Expert opinion: In ASD, pharmacotherapy and specifically dopamine antagonist drugs are often prescribed for challenging behaviors including aggression. The novel antipsychotics risperidone and aripiprazole have received most study in ASD and are FDA-approved for irritability in children with ASD over age 5 years; individuals with ASD are prone to weight gain, Type II diabetes and associated side effects. Low dose Loxapine has properties of classical and novel antipsychotics but importantly appears more weight neutral, and with promising use in adolescents and adults with ASD. Amitriptyline appears effective in ASD for irritability, aggression, gastrointestinal problems, and insomnia, in children, adolescents and adults however our adult data on amitriptyline in ASD is still in preparation for publication. Both Loxapine and amitriptyline may stimulate BDNF; further studies are warranted.

The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review.[Pubmed:28208695]

Int J Mol Sci. 2017 Feb 8;18(2). pii: ijms18020349.

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, Loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled Loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled Loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled Loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled Loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled Loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled Loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled Loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation.

Description

Loxapine Succinate is a D2DR and D4DR inhibitor, serotonergic receptor antagonist and also a dibenzoxazepine anti-psychotic agent.

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