Absorption, Distribution and Excretion
Amoxapine is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 1–2 hours after a single oral dose. 60–69% of the single oral dose of amoxapine is excreted in the urine, primarily as conjugated metabolites. 7–18% is excreted in the feces, primarily as unconjugated metabolites. Less than 5% is excreted unchanged in the urine. It is widely distributed throughout the body, with the highest concentrations in the lungs, spleen, kidneys, heart, and brain. Lower concentrations are detectable in the testes and muscles. Metabolism/Metabolites Amoxapine is almost entirely metabolized in the liver to the major metabolite 8-hydroxyamoxabine and the minor metabolite 7-hydroxyamoxabine. Both metabolites are pharmacologically inactive, with half-lives of approximately 30 hours and 6.5 hours, respectively. Amoxapine is almost entirely metabolized in the liver to the major metabolite 8-hydroxyamoxapane and the minor metabolite 7-hydroxyamoxapane. Both metabolites are pharmacologically inactive, with half-lives of approximately 30 hours and 6.5 hours, respectively. Elimination pathway: Following a single oral dose of amoxapine, 60-69% of the dose is excreted primarily in the urine as conjugated metabolites. 7-18% of the dose is excreted primarily in the feces as unconjugated metabolites. Less than 5% of the dose is excreted unchanged in the urine. Half-life: 8 hours.

Hepatotoxicity
A small number of patients taking amoxapine long-term may experience abnormal liver function, but these are usually mild, asymptomatic, and transient, and resolve with continued use. While there have been reports of clinically significant acute liver injury (without jaundice) caused by amoxapine, this is extremely rare. Published cases have all been mild, without jaundice, and asymptomatic liver injury. The injury typically appears within 1 to 4 weeks of starting treatment, with elevated serum enzymes indicating hepatocellular lesions. No immune hypersensitivity features or autoantibody formation were observed. Probability score: E (unlikely to be the cause of clinically significant liver injury).

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Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Since there is no published experience with amoxapine use during lactation, alternative medications may be preferred, especially for breastfed newborns or premature infants. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
Two cases of galactorrhea have been reported in non-lactating women taking amoxapine. The clinical significance of these findings for lactating women is unclear. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed. An observational study investigated the outcomes of 2,859 women who had taken antidepressants in the two years prior to pregnancy. Compared to women who did not take antidepressants during pregnancy, mothers who took antidepressants in all three stages of pregnancy were 37% less likely to breastfeed at discharge. Mothers who took antidepressants only in the third trimester were 75% less likely to breastfeed at discharge. Mothers who took antidepressants only in the first and second trimesters were not less likely to breastfeed at discharge. The specific antidepressants used by the mothers were not specified. A retrospective cohort study analyzed hospital electronic medical records from 2001 to 2008, comparing women who took antidepressants in late pregnancy (n = 575), women with mental illness but not taking antidepressants (n = 1552), and mothers not diagnosed with mental illness (n = 30,535). Results showed that women who took antidepressants were 37% less likely to breastfeed at discharge than women not diagnosed with mental illness, but there was no significant difference in the likelihood of breastfeeding compared to untreated mothers with mental illness. None of the mothers were taking amoxapine. A study of 80,882 Norwegian mother-infant pairs from 1999 to 2008 showed that 392 women reported starting antidepressants postpartum, and another 201 women reported starting antidepressants during pregnancy. Compared to a control group not exposed to antidepressants, taking antidepressants in late pregnancy was associated with a 7% lower rate of breastfeeding initiation, but had no effect on the duration of breastfeeding or the rate of exclusive breastfeeding. Compared to the control group who were not exposed to antidepressants, initiating or restarting antidepressant use postpartum was associated with a 63% lower rate of primary breastfeeding at 6 months, a 51% lower rate of any form of breastfeeding, and a 2.6-fold increased risk of abrupt cessation of breastfeeding. No specific antidepressant was mentioned.

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Protein Binding
In vitro studies showed that amoxapine binds to approximately 90% of human plasma proteins.

Amoxapine may cause developmental toxicity depending on state or federal labeling requirements. Amoxapine is a dibenzoxazole compound with a chlorine substituent at position 2 and a piperazine-1-yl group at position 11. It has antidepressant, adrenergic reuptake inhibitor, dopaminergic antagonist, serotonin reuptake inhibitor, and anti-aging effects. Amoxapine is an N-demethylated derivative of the antipsychotic drug loxapine and belongs to the dibenzoxazole derivative tricyclic antidepressant (TCA) class. TCAs have a structure similar to phenothiazine drugs, containing a tricyclic ring system with an alkylamine substituent on the central ring. In non-depressed patients, amoxapine does not affect mood or wakefulness but may cause sedation. Amoxapine has a positive effect on mood in patients with depression. Tricyclic antidepressants (TCAs) are potent serotonin and norepinephrine reuptake inhibitors. Furthermore, long-term use of TCAs downregulates cortical β-adrenergic receptors and sensitizes postsynaptic serotonergic receptors. The antidepressant effect of TCAs is thought to be due to an overall enhancement of serotonergic neurotransmission. TCAs also block histamine H1 receptors, α1-adrenergic receptors, and muscarinic receptors, which explains their sedative, hypotensive, and anticholinergic effects (e.g., blurred vision, dry mouth, constipation, urinary retention), respectively. For a complete list of side effects, please see the Toxicity section below. Amoxapine can be used to treat neurotic depression, reactive depression, endogenous depression, psychotic depression, and mixed symptoms of depression and anxiety or agitation. Amoxapine is a tricyclic antidepressant. Amoxapine is a tetracyclic antidepressant used to relieve depressive symptoms caused by reactive depression or psychotic depression. Mild elevations of serum transaminases are rare during amoxapine treatment, and clinically significant acute liver injury may occur in very rare cases. Amoxapine is a dibenzoxazole tricyclic antidepressant. It exerts its antidepressant effect by inhibiting the reuptake of norepinephrine (and a lesser degree of serotonin) at adrenergic nerve endings and by blocking the dopamine receptor response to dopamine. This drug is used to treat depressive symptoms and may cause tardive dyskinesia. Amoxapine can also bind to alpha-adrenergic, histaminergic, and cholinergic receptors, which explains many of its side effects. Amoxapine is an N-demethylated derivative of the antipsychotic drug loxapine and belongs to the dibenzoxazole-azazepine tricyclic antidepressant (TCA) class. TCAs have a structure similar to phenothiazines, containing a tricyclic ring system with an alkylamine substituent attached to the central ring. In non-depressed patients, amoxapine does not affect mood or arousal but may cause sedation. In depressive patients, amoxapine has a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Furthermore, long-term use of tricyclic antidepressants (TCAs) downregulates cortical β-adrenergic receptors and sensitizes postsynaptic serotonergic receptors. The antidepressant effect of TCAs is thought to be due to an overall enhancement of serotonergic neurotransmission. TCAs also block histamine H1 receptors, α1-adrenergic receptors, and muscarinic receptors, which explains their sedative, hypotensive, and anticholinergic effects (e.g., blurred vision, dry mouth, constipation, urinary retention), respectively. For a complete list of side effects, please see the Toxicity section below. Amoxapine is used to treat neurosis and reactive depression, endogenous depression and psychotic depression, as well as mixed symptoms of depression and anxiety or agitation. Amoxapine is an N-demethylated derivative of the antipsychotic drug loxapine, and its mechanism of action is by blocking the reuptake of norepinephrine, serotonin, or both; it also blocks dopamine receptors. Amoxapine is used to treat depression.

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Indications
For the relief of depressive symptoms in patients with neurotic or reactive depression, as well as endogenous and psychotic depression. It can also be used to treat depression accompanied by anxiety or agitation.

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Mechanism of Action
Amoxapine works by reducing the reuptake of norepinephrine and serotonin (5-HT).

C17H16CLN3O

313.78

313.098

14028-44-5

Amoxapine-d8;1189671-27-9

2170

White to light yellow solid powder

1.37g/cm3

469.9ºC at 760mmHg

175-1760C

238ºC

5.32E-09mmHg at 25°C

1.685

3.131

1

3

1

22

424

0

ClC1C([H])=C([H])C2=C(C=1[H])C(=NC1=C([H])C([H])=C([H])C([H])=C1O2)N1C([H])([H])C([H])([H])N([H])C([H])([H])C1([H])[H]

QWGDMFLQWFTERH-UHFFFAOYSA-N

InChI=1S/C17H16ClN3O/c18-12-5-6-15-13(11-12)17(21-9-7-19-8-10-21)20-14-3-1-2-4-16(14)22-15/h1-6,11,19H,7-10H2

8-chloro-6-piperazin-1-ylbenzo[b][1,4]benzoxazepine

Asendin AmoxanAsendis AdisenDefanyl Demolox OxcapOxamine Amolife

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~8.33 mg/mL (~26.55 mM)

Solubility in Formulation 1: ≥ 1.56 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.6 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 1.56 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.6 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 1.56 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.6 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)