Clinical data
Trade namesAsendin, others
License data
Routes of
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding90%[5]
MetabolismHepatic (cytochrome P450 system)[4]
Elimination half-life8–10 hours (30 hours for chief active metabolite)[5]
ExcretionRenal (60%), feces (18%)[4]
  • 2-chloro-11-(piperazin-1-yl)dibenzo[b,f][1,4]oxazepine
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.034.411 Edit this at Wikidata
Chemical and physical data
Molar mass313.79 g·mol−1
3D model (JSmol)
  • Clc2ccc1Oc4c(/N=C(\c1c2)N3CCNCC3)cccc4
  • 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 checkY

Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1980, approximately 10 to 20 years after most of the other TCAs were introduced in the United States.[6]

Medical uses

Amoxapine is used in the treatment of major depressive disorder. Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days.[7][8] In excess of 80% of patients that do respond to amoxapine are reported to respond within two weeks of the beginning of treatment.[9] It also has properties similar to those of the atypical antipsychotics,[10][11][12] and may behave as one[13][14] and thus may be used in the treatment of schizophrenia off-label. Despite its apparent lack of extrapyramidal side effects in patients with schizophrenia it has been found to worsen motor function in a study of three patients with Parkinson's disease and psychosis.[15]


As with all FDA-approved antidepressants it carries a black-box warning about the potential of an increase in suicidal thoughts or behaviour in children, adolescents and young adults under the age of 25.[4] Its use is also advised against in individuals with known hypersensitivities to either amoxapine or other ingredients in its oral formulations.[4] Its use is also recommended against in the following disease states:[4]

Its use is also advised against in individuals concurrently on monoamine oxidase inhibitors or if they have been on one in the past 14 days and in individuals on drugs that are known to prolong the QT interval (e.g. ondansetron, citalopram, pimozide, sertindole, ziprasidone, haloperidol, chlorpromazine, thioridazine, etc.).[4]


Its use in breastfeeding mothers not recommended as it is excreted in breast milk and the concentration found in breast milk is approximately a quarter that of the maternal serum level.[7][16]

Side effects

Adverse effects by incidence:[4][17]
Note: Serious (that is, those that can either result in permanent injury or are irreversible or are potentially life-threatening) are written in bold text.

Very common (>10% incidence) adverse effects include:

Common (1–10% incidence) adverse effects include:

Uncommon/Rare (<1% incidence) adverse effects include:

Unknown incidence or relationship to drug treatment adverse effects include:

It tends to produce less anticholinergic effects, sedation and weight gain than some of the earlier TCAs (e.g. amitriptyline, clomipramine, doxepin, imipramine, trimipramine).[18] It may also be less cardiotoxic than its predecessors.[19]


Main article: Tricyclic antidepressant overdose

It is considered particularly toxic in overdose,[20] with a high rate of renal failure (which usually takes 2–5 days), rhabdomyolysis, coma, seizures and even status epilepticus.[19] Some believe it to be less cardiotoxic than other TCAs in overdose, although reports of cardiotoxic overdoses have been made.[7][17]



See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles

Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter 58 Human [22]
NETTooltip Norepinephrine transporter 16 Human [22]
DATTooltip Dopamine transporter 4,310 Human [22]
5-HT2A 0.5 Human [23]
5-HT2C 2.0 Monkey [24]
5-HT6 6.0–50 Human [24][25]
5-HT7 41 Monkey [24]
α1 50 Human [26]
α2 2,600 Human [26]
D2 3.6–160 Human [27][23][26]
D3 11 Human [23]
D4 2.0–40 Human [23]
H1 7.9–25 Human [28][26]
H3 >100,000 Human [28]
H4 6,310 Human [28]
mAChTooltip Muscarinic acetylcholine receptor 1,000 Human [26]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Amoxapine possesses a wide array of pharmacological effects. It is a moderate and strong reuptake inhibitor of serotonin and norepinephrine, respectively,[22] and binds to the 5-HT2A,[29] 5-HT2B,[30] 5-HT2C,[29] 5-HT3,[31] 5-HT6,[24] 5-HT7,[24] D2,[26] α1-adrenergic,[26] D3,[27] D4,[27] and H1 receptors[26] with varying but significant affinity, where it acts as an antagonist (or inverse agonist depending on the receptor in question) at all sites. It has weak but negligible affinity for the dopamine transporter and the 5-HT1A,[31] 5-HT1B,[31] D1,[32] α2-adrenergic,[26] H4,[33] mACh,[26] and GABAA receptors,[32] and no affinity for the β-adrenergic receptors or the allosteric benzodiazepine site on the GABAA receptor.[32] Amoxapine is also a weak GlyT2 blocker,[34] as well as a weak (Ki = 2.5 μM, EC50 = 0.98 μM) δ-opioid receptor partial agonist.[35]

7-Hydroxyamoxapine, a major active metabolite of amoxapine, is a more potent dopamine receptor antagonist and contributes to its neuroleptic efficacy,[10] whereas 8-hydroxyamoxapine is a norepinephrine reuptake inhibitor but a stronger serotonin reuptake inhibitor and helps to balance amoxapine's ratio of serotonin to norepinephrine transporter blockade.[36]


Amoxapine is metabolised into two main active metabolites: 7-hydroxyamoxapine and 8-hydroxyamoxapine.[37]

Compound[37][38][39] t1/2 (hr)[40] tmax (hr) CSS (ng/mL) Protein binding[4] Vd[4] Excretion[4]
Amoxapine 8 1-2 17-93 ng/mL (divided dosing), 13-209 ng/mL (single daily dosing) 90% 0.9-1.2 L/kg Urine (60%), feces (18%)
8-hydroxyamoxapine 30 5.3 (single dosing) 158-512 ng/mL (divided dosing), 143-593 ng/mL (single dose) ? ? ?
7-hydroxyamoxapine 6.5 2.6-5.4 (single dosing) ? ? ? ?


Society and culture

Brand names

Brand names for amoxapine include (where † denotes discontinued brands):[7][41]

See also


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  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". FDA. Retrieved 22 October 2023.
  3. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  4. ^ a b c d e f g h i j k "Asendin, (amoxapine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 November 2013.
  5. ^ a b Kinney JL, Evans RL (September–October 1982). "Evaluation of amoxapine". Clinical Pharmacy. 1 (5): 417–424. PMID 6764165.
  6. ^ National Center for Drugs and Biologics (U.S.) (1984). Approved Prescription Drug Products with Therapeutic Equivalence Evaluations (5th, Cumulative Supplement 3 ed.). Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Food and Drug Administration. p. IV-9.
  7. ^ a b c d Amoxapine. London, UK: Pharmaceutical Press. 30 January 2013. Retrieved 26 November 2013. ((cite book)): |work= ignored (help)
  8. ^ Ban TA, Fujimori M, Petrie WM, Ragheb M, Wilson WH (1982). "Systematic studies with amoxapine, a new antidepressant". International Pharmacopsychiatry. 17 (1): 18–27. doi:10.1159/000468553. PMID 7045016.
  9. ^ Product Information: Asendin(R), amoxapine tablets. Physicians' Desk Reference (electronic version), MICROMEDEX, Inc, Englewood, CO, USA, 1999.
  10. ^ a b Cohen BM, Harris PQ, Altesman RI, Cole JO (September 1982). "Amoxapine: neuroleptic as well as antidepressant?". The American Journal of Psychiatry. 139 (9): 1165–1167. doi:10.1176/ajp.139.9.1165. PMID 6126130.
  11. ^ Kapur S, Cho R, Jones C, McKay G, Zipursky RB (May 1999). "Is amoxapine an atypical antipsychotic? Positron-emission tomography investigation of its dopamine2 and serotonin2 occupancy". Biological Psychiatry. 45 (9): 1217–1220. doi:10.1016/S0006-3223(98)00204-2. PMID 10331115. S2CID 21407817.
  12. ^ Wadenberg MG, Sills TL, Fletcher PJ, Kapur S (April 2000). "Antipsychoticlike effects of amoxapine, without catalepsy, using the prepulse inhibition of the acoustic startle reflex test in rats". Biological Psychiatry. 47 (7): 670–676. doi:10.1016/S0006-3223(99)00267-X. PMID 10745061. S2CID 27619436.
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