QuickView for amoxapine (compound)

Summary
General Info

PubChem

PubChem Compound 2170

Name:	Amoxapine
PubChem Compound ID:	2170
Description:	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.
Molecular formula:	C₁₇H₁₆ClN₃O
Molecular weight:	313.781 g/mol
Synonyms:	NCGC00015004-02; NCGC00015004-01; AMOXEPINE; EU-0100116; Prestwick1_000102; 14028-44-5; Demolox; SPBio_001150; KBio1_000236; DIBENZ(b,f)(1,4)OXAZEPINE, 2-CHLORO-11-(1-PIPERAZINYL)-. show more » NCGC00015004-02; NCGC00015004-01; AMOXEPINE; EU-0100116; Prestwick1_000102; 14028-44-5; Demolox; SPBio_001150; KBio1_000236; DIBENZ(b,f)(1,4)OXAZEPINE, 2-CHLORO-11-(1-PIPERAZINYL)-; Desmethylloxapin; Amoxapinum [INN-Latin]; CL 67772; Moxadil; Spectrum2_001245; MLS000069371; EINECS 237-867-1; SMR000058416; 2-Chloro-11-(1-piperazinyl)dibenz(b,f)(1,4)oxazepine; Lopac-A-129; Amoxapine; Prestwick0_000102; Asendin; SPBio_002023; Asendin (TN); Amoxapine (JP15/USP); DivK1c_000236; Amoxapina [INN-Spanish]; CL-67772; 2-Chlor-11-(1-piperazinyl)dibenz(b,f)(1,4)oxazepin; Dibenz[b,f][1,4]oxazepine, 2-chloro-11-(1-piperazinyl)-; KBio2_000926; KBio3_001874; D00228; Amoxapine [USAN:BAN:INN:JAN]; Spectrum3_001067; Spectrum_000446; Prestwick_503; KBioSS_000926; BRN 0832057; Spectrum4_001218; NINDS_000236; KBioGR_001656; CAS-14028-44-5; KBio2_003494; Amoxan; KBio2_006062 show less «

DrugBank

Identification

Name:	Amoxapine
Name (isomeric):	DB00543
Drug Type:	small molecule
Description:	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.
Synonyms:	Amoxepine
Brand:	Defanyl, Ascendin, Demolox, Asendis, Moxadil
Category:	Neurotransmitter Uptake Inhibitors, Adrenergic Uptake Inhibitors, Dopamine Antagonists, Antidepressive Agents, Second-Generation, Serotonin Uptake Inhibitors
CAS number:	14028-44-5

Pharmacology

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.
Pharmacology:	Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzodiazepines, dibenzocycloheptenes, and dibenzoxepines. It has a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of nor-epinephirine and serotonin... show more » Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzodiazepines, dibenzocycloheptenes, and dibenzoxepines. It has a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of nor-epinephirine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Clinical studies have demonstrated that amoxapine has a more rapid onset of action than either amitriptyline or imipramine show less «
Mechanism of Action:	Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).
Absorption:	Rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations occur within 1-2 hours of oral administration of a single dose.
Protein binding:	In vitro tests show that amoxapine binding to human plasma proteins is approximately 90%.
Biotransformation:	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
Toxicity:	Toxic manifestations of amoxapine overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects, particularly grand mal convulsions, occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial amoxapine overdosage in some cases. Renal failure may develop two to five days after toxic overdose in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomuolysis and myolobinurla is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid alcohol.

Take with food to reduce irritation.

Drug interaction:

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Methoxamine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of methoxamine.
Ephedrine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of ephedrine.
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amoxapine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if rifabutin is initiated, discontinued or dose changed.
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Methoxamine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of methoxamine.
Ephedrine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of ephedrine.
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amoxapine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if rifabutin is initiated, discontinued or dose changed.
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias
Orciprenaline	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of orciprenaline.
Isoproterenol	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of isoproterenol.
Fenoterol	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of fenoterol.
Cimetidine	Cimetidine may increase the effect of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if cimetidine is initiated, discontinued or dose changed.
Phenylephrine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of phenylephrine.
Tranylcypromine	Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Fluoxetine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amoxapine if fluoxetine is initiated, discontinued or dose changed.
Phenylpropanolamine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of phenylpropanolamine.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Fluvoxamine	The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amoxapine if fluvoxamine is initiated, discontinued or dose changed.
Epinephrine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of epinephrine.
Mephentermine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of mephentermine.
Clonidine	The tricyclic antidepressant, amoxapine, decreases the effect of clonidine.
Pseudoephedrine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of pseudoephedrine.
Pirbuterol	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of pirbuterol.
Terbutaline	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of terbutaline.
Norepinephrine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of norepinephrine.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Butabarbital	Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like amoxipine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Atazanavir	Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if atazanavir if initiated, discontinued or dose changed.
Phenelzine	Possibility of severe adverse effects
Moclobemide	Possible severe adverse reaction with this combination
Trimethobenzamide	Trimethobenzamide and Amoxapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Galantamine	Possible antagonism of action
Guanethidine	The tricyclic antidepressant, amoxapine, decreases the effect of guanethidine.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Triprolidine	Triprolidine and Amoxapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Isocarboxazid	Possibility of severe adverse effects
Rivastigmine	Possible antagonism of action
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Amoxapine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ritonavir	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if ritonavir if initiated, discontinued or dose changed.
Sibutramine	Increased risk of CNS adverse effects
Terbinafine	Terbinafine may reduce the metabolism and clearance of Amoxapine. Consider alternate therapy or monitor for therapeutic/adverse effects of Amoxapine if Terbinafine is initiated, discontinued or dose changed.
Dopamine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of dopamine.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trospium	Trospium and Amoxapine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Donepezil	Possible antagonism of action
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Rifampin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, amoxapine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if rifampin is initiated, discontinued or dose changed.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and amoxapine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Tramadol	Tramadol increases the risk of serotonin syndrome and seizures.
Procaterol	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of procaterol.
Altretamine	Risk of severe hypotension
Salbutamol	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of salbutamol.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Butalbital	Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants amoxapine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Metaraminol	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of metaraminol.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Dobutamine	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of dobutamine.
Rasagiline	Possibility of severe adverse effects
Ephedra	The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of ephedra.

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Targets

Sodium-dependent noradrenaline transporter

Sodium-dependent serotonin transporter

D(2) dopamine receptor

D(1A) dopamine receptor

Alpha-2A adrenergic receptor

Alpha-1A adrenergic receptor

Muscarinic acetylcholine receptor M1

Gamma-aminobutyric-acid receptor subunit alpha-1

Enzymes

Cytochrome P450 2D6

Carriers

Alpha-1-acid glycoprotein 1