Loxapine Succinate

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Cat Number

API0232114

CAS Number

27833-64-3

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Product Detail Description Scientific Support Customer Q&A

CAS Number

27833-64-3

EINECS

248-682-0

Storage

Store at room temperature

Synonyms

Loxapac; Cloxazepin; Daxolin; CL 71563; DTXSID3045227; X59SG0MRYU; NSC-759578

Molecular Formula

C22H24ClN3O5

Molecular Weight

445.9

Smiles

CN1CCN(CC1)C2=NC3=CC=CC=C3OC4=C2C=C(C=C4)Cl.C(CC(=O)O)C(=O)O

Appearance

White to off-white powder

Melting Point

150-152°C

Boiling Point

458.6°C at 760 mmHg

General Description

Loxapine succinate is a dibenzoxazepine derivative and a first-generation antipsychotic belonging to the tricyclic class. Its structure contains an amide linkage and a piperazine ring, distinguishing it from the phenothiazines. The succinate salt is formed from loxapine and succinic acid, enhancing water solubility without altering the pharmacological profile. Loxapine itself has a nitrogen atom at the 10-position replacing the carbon of the phenothiazine ring.

Mechanism of Action

Loxapine exerts its antipsychotic effect primarily by antagonizing dopamine D2 receptors in the mesolimbic and mesocortical pathways. It also blocks serotonin 5-HT2A, histamine H1, and alpha-1 adrenergic receptors, contributing to its sedative and hypotensive effects. The drug has high affinity for D2 and 5-HT2A receptors, similar to many atypical antipsychotics, but is classified as typical due to its extrapyramidal side effect profile. The metabolite amoxapine has additional norepinephrine reuptake inhibitory activity.

Application

Loxapine is indicated for the management of schizophrenia and bipolar I disorder (acute manic or mixed episodes). It is also used off-label for agitated or aggressive behavior in dementia and other psychiatric conditions.

This narrative review evaluates inhaled loxapine for acute agitation in psychiatric disorders. Efficacy is supported by one phase II and two phase III trials in schizophrenia and bipolar disorder, and case series suggest potential benefit in borderline personality disorder and dual diagnosis. The drug requires patient cooperation and is not recommended for severe agitation in uncooperative patients. Bronchospasm is a serious risk, necessitating careful patient assessment. Cost is higher than oral or intramuscular alternatives. Inhaled loxapine is effective and generally well tolerated, but its use requires careful patient selection and monitoring.

Fig. 1 Management of acute agitation: the suggested position of intranasal FGA loxapine (adapted and modified from Schleifer. (de Berardis D, et al., 2017)

References

de Berardis D, et al. The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review. Int J Mol Sci. 2017;18(2):349.

Does Loxapine Succinate require protection from light during storage?

Yes, it is photosensitive. UV exposure can cause photodegradation and discoloration. Store in light-resistant containers, preferably amber glass or original opaque packaging.

What is the recommended storage temperature for Loxapine Succinate?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, which can accelerate oxidative degradation of the dibenzoxazepine ring.

Is Loxapine Succinate hygroscopic, and how is this managed?

It is slightly hygroscopic. Under high humidity (>70% RH), it may absorb moisture and clump. Storage in tightly sealed containers with desiccant is recommended.

How is the impurity loxapine N-oxide (an oxidative degradation product) monitored?

This degradation product is quantified using a stability-indicating HPLC method, ensuring it remains below ICH qualification thresholds.