Absorption, Distribution and Excretion
Rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations occur within 1-2 hours of oral administration of a single dose.
60-69% of a single orally administered dose of amoxapine is excreted in urine, principally as conjugated metabolites. 7-18% of the dose is excrete feces mainly as unconjugated metabolites. Less than 5% of the dose is excreted as unchanged drug in urine.
Widely distributed in body tissues with highest concentrations found in lungs, spleen, kidneys, heart, and brain. Lower concentrations can be detected in testes and muscle.

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Metabolism / Metabolites
Amoxapine is almost completely metabolized in the liver to its major metabolite, 8-hydroxyamoxapine, and a minor metabolite, 7-hydroxyamoxapine. Both metabolites are phamacologically inactive and have half-lives of approximately 30 and 6.5 hours, respectively.
Amoxapine is almost completely metabolized in the liver to its major metabolite, 8-hydroxyamoxapine, and a minor metabolite, 7-hydroxyamoxapine. Both metabolites are phamacologically inactive and have half-lives of approximately 30 and 6.5 hours, respectively.
Route of Elimination: 60-69% of a single orally administered dose of amoxapine is excreted in urine, principally as conjugated metabolites. 7-18% of the dose is excrete feces mainly as unconjugated metabolites. Less than 5% of the dose is excreted as unchanged drug in urine.
Half Life: 8 hours

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Biological Half-Life
8 hours

Hepatotoxicity
Liver test abnormalities occur in a small proportion of patients on long term therapy with amoxapine, but elevations are usually mild, asymptomatic and transient, reversing even with continuation of medication. Instances of clinically apparent acute liver injury without jaundice have been reported due to amoxapine, but have been quite rare. Published cases have been mild, anicteric and asymptomatic. The onset of injury was within 1 to 4 weeks of starting, and the pattern of serum enzyme elevations was hepatocellular. Immunoallergic features and autoantibody formation were not present.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because there is no published experience with amoxapine during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Two cases of galactorrhea have been reported in nonbreastfeeding women who were taking amoxapine. The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified.
A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis. None of the mothers were taking amoxapine.
In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.

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Protein Binding
In vitro tests show that amoxapine binding to human plasma proteins is approximately 90%.

Amoxapine can cause developmental toxicity according to state or federal government labeling requirements.
Amoxapine is a dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position. It has a role as an antidepressant, an adrenergic uptake inhibitor, a dopaminergic antagonist, a serotonin uptake inhibitor and a geroprotector.
Amoxapine, the N-demethylated derivative of the antipsychotic agent loxapine, is a dibenzoxazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amoxapine does not affect mood or arousal, but may cause sedation. In depressed individuals, amoxapine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amoxapine may be used to treat neurotic and reactive depressive disorders, endogenous and psychotic depression, and mixed symptoms of depression and anxiety or agitation.
Amoxapine is a Tricyclic Antidepressant.
Amoxapine is a tetracyclic antidepressant used for relief of symptoms of depression caused by either reactive or psychotic depression. Amoxapine has been associated with a low rate of minor serum aminotransferase elevations during treatment and to very rare instances of clinically apparent acute liver injury.
Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class. Amoxapine exerts its antidepressant effect by inhibiting the re-uptake of norepinephrine and, to a lesser degree, of serotonin, at adrenergic nerve endings and blocks the response of dopamine receptors to dopamine. This drug is used to treat symptoms of depression and may cause tardive dyskinesia. Amoxapine also binds to alpha-adrenergic, histaminergic, and cholinergic receptors which accounts for many of the side effects seen with this agent.
Amoxapine, the N-demethylated derivative of the antipsychotic agent loxapine, is a dibenzoxazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amoxapine does not affect mood or arousal, but may cause sedation. In depressed individuals, amoxapine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H₁ receptors, α₁-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amoxapine may be used to treat neurotic and reactive depressive disorders, endogenous and psychotic depression, and mixed symptoms of depression and anxiety or agitation.
The N-demethylated derivative of the antipsychotic agent LOXAPINE that works by blocking the reuptake of norepinephrine, serotonin, or both; it also blocks dopamine receptors. Amoxapine is used for the treatment of depression.

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Drug Indication
For the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. May also be used to treat depression accompanied by anxiety or agitation.

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Mechanism of Action
Amoxapine acts by decreasing 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.)