Amoxapine

Last updated

Amoxapine
Amoxapine.svg
Amoxapine ball-and-stick model.png
Clinical data
PronunciationA-mox-a-peen [1]
Trade names Asendin, others
AHFS/Drugs.com Monograph
MedlinePlus a682202
License data
Routes of
administration 		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability >60% [3]
Protein binding 90% [4]
Metabolism Hepatic (cytochrome P450 system) [3]
Elimination half-life 8–10 hours (30 hours for chief active metabolite) [4]
Excretion Renal (60%), feces (18%) [3]
Identifiers
  • 2-chloro-11-(piperazin-1-yl)dibenzo[b,f][1,4]oxazepine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.034.411 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H16ClN3O
Molar mass 313.79 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 Yes check.svgY
  • Key:QWGDMFLQWFTERH-UHFFFAOYSA-N Yes check.svgY
   (verify)

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. [5]

Contents

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. [6] [7] In excess of 80% of patients that do respond to amoxapine are reported to respond within two weeks of the beginning of treatment. [8] It also has properties similar to those of the atypical antipsychotics, [9] [10] [11] and may behave as one [12] [13] 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 exacerbate motor symptoms in patients with Parkinson's disease and psychosis. [14]

Contraindications

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. [3] Its use is also advised against in individuals with known hypersensitivities to either amoxapine or other ingredients in its oral formulations. [3] Its use is also recommended against in the following disease states: [3]

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.). [3]

Lactation

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. [6] [15]

Side effects

Adverse effects by incidence: [3] [16]
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). [17] It may also be less cardiotoxic than its predecessors. [18]

Overdose

It is considered particularly toxic in overdose, [19] with a high rate of renal failure (which usually takes 2–5 days), rhabdomyolysis, coma, seizures and even status epilepticus. [18] Some believe it to be less cardiotoxic than other TCAs in overdose, although reports of cardiotoxic overdoses have been made. [6] [16]

Pharmacology

Pharmacodynamics

Amoxapine [20]
SiteKi (nM)SpeciesRef
SERT Tooltip Serotonin transporter58Human [21]
NET Tooltip Norepinephrine transporter16Human [21]
DAT Tooltip Dopamine transporter4,310Human [21]
5-HT2A 0.5Human [22]
5-HT2C 2.0Monkey [23]
5-HT6 6.0–50Human [23] [24]
5-HT7 41Monkey [23]
α1 50Human [25]
α2 2,600Human [25]
D2 3.6–160Human [26] [22] [25]
D3 11Human [22]
D4 2.0–40Human [22]
H1 7.9–25Human [27] [25]
H2 NDNDND
H3 >100,000Human [27]
H4 6,310Human [27]
mACh Tooltip Muscarinic acetylcholine receptor1,000Human [25]
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, [21] and binds to the 5-HT2A, [28] 5-HT2B, [29] 5-HT2C, [28] 5-HT3, [30] 5-HT6, [23] 5-HT7, [23] D2, [25] α1-adrenergic, [25] D3, [26] D4, [26] and H1 receptors [25] 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, [30] 5-HT1B, [30] D1, [31] α2-adrenergic, [25] H4, [32] mACh, [25] and GABAA receptors, [31] and no affinity for the β-adrenergic receptors or the allosteric benzodiazepine site on the GABAA receptor. [31] Amoxapine is also a weak GlyT2 blocker, [33] as well as a weak (Ki = 2.5 μM, EC50 = 0.98 μM) δ-opioid receptor partial agonist. [34]

7-Hydroxyamoxapine, a major active metabolite of amoxapine, is a more potent dopamine receptor antagonist and contributes to its neuroleptic efficacy, [9] 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. [35]

Pharmacokinetics

Amoxapine is metabolised into two main active metabolites: 7-hydroxyamoxapine and 8-hydroxyamoxapine. [36]

Amoxapine Amoxapine.svg
Amoxapine
7-hydroxyamoxapine 7-Hydroxyamoxapine.svg
7-hydroxyamoxapine
8-hydroxyamoxapine 8-Hydroxyamoxapine.svg
8-hydroxyamoxapine
Compound [36] [37] [38] t1/2 (hr) [39] tmax (hr)CSS (ng/mL)Protein binding [3] Vd [3] Excretion [3]
Amoxapine81-217-93 ng/mL (divided dosing), 13-209 ng/mL (single daily dosing)90%0.9-1.2 L/kgUrine (60%), feces (18%)
8-hydroxyamoxapine 305.3 (single dosing)158-512 ng/mL (divided dosing), 143-593 ng/mL (single dose) ? ? ?
7-hydroxyamoxapine 6.52.6-5.4 (single dosing) ? ? ? ?

Where:

Society and culture

Brand names

Brand names for amoxapine include (where † denotes discontinued brands): [6] [40]

See also

Related Research Articles

An anxiolytic is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms.

<span class="mw-page-title-main">Tricyclic antidepressant</span> Class of medications

Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs and SNRIs. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms.
Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use do not appear to generally outweigh the side effects. It is taken orally.

<span class="mw-page-title-main">Tetracyclic antidepressant</span> Class of pharmaceutical drugs

Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their tetracyclic chemical structure, containing four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.

<span class="mw-page-title-main">Loxapine</span> Antipsychotic medication

Loxapine, sold under the brand names Loxitane and Adasuve among others, is a tricyclic antipsychotic medication used primarily in the treatment of schizophrenia. The medicine is a member of the dibenzoxazepine class and structurally very similar to clozapine. Several researchers have argued that loxapine, initially classified as a typical antipsychotic, behaves as an atypical antipsychotic.

<span class="mw-page-title-main">Mirtazapine</span> Antidepressant medication

Mirtazapine, sold under the brand name Remeron amongst others, is an atypical tetracyclic antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is often used in cases of depression complicated by anxiety or insomnia. The effectiveness of mirtazapine is comparable to other commonly prescribed antidepressants. It is taken by mouth.

<span class="mw-page-title-main">Azapirone</span> Drug class of psycotropic drugs

Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).

<span class="mw-page-title-main">Dopamine antagonist</span> Drug which blocks dopamine receptors

A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

<span class="mw-page-title-main">Desipramine</span> Antidepressant

Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression. It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activities such as weak serotonin reuptake inhibitory, α1-blocking, antihistamine, and anticholinergic effects. The drug is not considered a first-line treatment for depression since the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants, which have fewer side effects and are safer in overdose.

<span class="mw-page-title-main">Trimipramine</span> Antidepressant

Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or "second-generation" TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities.

<span class="mw-page-title-main">Dosulepin</span> Antidepressant

Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the United Kingdom, but it is no longer widely used due to its relatively high toxicity in overdose without therapeutic advantages over other TCAs. It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has other activities including antihistamine, antiadrenergic, antiserotonergic, anticholinergic, and sodium channel-blocking effects.

<span class="mw-page-title-main">Mianserin</span> Antidepressant

Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant that is used primarily in the treatment of depression in Europe and elsewhere in the world. It is a tetracyclic antidepressant (TeCA). Mianserin is closely related to mirtazapine, both chemically and in terms of its actions and effects, although there are significant differences between the two drugs.

<span class="mw-page-title-main">Opipramol</span> Drug used to treat depressive and anxiety disorders

Opipramol, sold under the brand name Insidon among others, is an anxiolytic and tricyclic antidepressant that is used throughout Europe. Despite chemically being a tricyclic dibenzazepine (iminostilbene) derivative similar to imipramine, opipramol is not a monoamine reuptake inhibitor like most other tricyclic antidepressants, and instead, uniquely among antidepressants, acts primarily as a SIGMAR1 agonist. It was developed by Schindler and Blattner in 1961.

<span class="mw-page-title-main">Serotonin receptor agonist</span> Neurotransmission-modulating substance

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

5-HT<sub>1A</sub> receptor Serotonin receptor protein distributed in the cerebrum and raphe nucleus

The serotonin 1A receptor is a subtype of serotonin receptors, or 5-HT receptors, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.

<span class="mw-page-title-main">Vilazodone</span> Medication used to treat major depressive disorder

Vilazodone, sold under the brand name Viibryd among others, is a medication used to treat major depressive disorder. It is classified as a serotonin modulator and is taken by mouth.

<span class="mw-page-title-main">Roxindole</span> Dopaminergic & serotonergic drug developed for schizophrenia treatment

Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed by Merck KGaA for the treatment of schizophrenia. In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects. As a result, roxindole was further researched for the treatment of depression instead. It has also been investigated as a therapy for Parkinson's disease and prolactinoma.

<span class="mw-page-title-main">Levofenfluramine</span> Non-marketed drug of the amphetamine class

Levofenfluramine (INN), or (−)-3-trifluoromethyl-N-ethylamphetamine, also known as (−)-fenfluramine or (R)-fenfluramine, is a drug of the amphetamine family that, itself (i.e., in enantiopure form), was never marketed. It is the levorotatory enantiomer of fenfluramine, the racemic form of the compound, whereas the dextrorotatory enantiomer is dexfenfluramine. Both fenfluramine and dexfenfluramine are anorectic agents that have been used clinically in the treatment of obesity (and hence, levofenfluramine has been as well since it is a component of fenfluramine). However, they have since been discontinued due to reports of causing cardiovascular conditions such as valvular heart disease and pulmonary hypertension, adverse effects that are likely to be caused by excessive stimulation of 5-HT2B receptors expressed on heart valves.

<span class="mw-page-title-main">8-Hydroxyamoxapine</span> Chemical compound

8-Hydroxyamoxapine is an active metabolite of the antidepressant drug amoxapine (Asendin). It contributes to amoxapine's pharmacology. It is a serotonin-norepinephrine reuptake inhibitor (SNRI) with similar norepinephrine, but more serotonin, reuptake inhibition as its parent compound. It plays a part in balancing amoxapine's ratio of serotonin to norepinephrine transporter blockage.

References

  1. ↑ "Amoxapine: Indications, Side Effects, Warnings -Drugs.com". Drugs.com. 6 November 2013. Retrieved 26 November 2013.
  2. ↑ 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.
  3. 1 2 3 4 5 6 7 8 9 10 11 "Asendin, (amoxapine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 November 2013.
  4. 1 2 Kinney JL, Evans RL (September–October 1982). "Evaluation of amoxapine". Clinical Pharmacy. 1 (5): 417–424. PMID   6764165.
  5. ↑ 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.
  6. 1 2 3 4 Amoxapine. 30 January 2013. Retrieved 26 November 2013.{{cite book}}: |work= ignored (help)
  7. ↑ 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.
  8. ↑ Product Information: Asendin(R), amoxapine tablets. Physicians' Desk Reference (electronic version), MICROMEDEX, Inc, Englewood, CO, USA, 1999.
  9. 1 2 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ Apiquian R, Fresan A, Ulloa RE, de la Fuente-Sandoval C, Herrera-Estrella M, Vazquez A, et al. (December 2005). "Amoxapine as an atypical antipsychotic: a comparative study vs risperidone". Neuropsychopharmacology. 30 (12): 2236–2244. doi: 10.1038/sj.npp.1300796 . PMID   15956984.
  13. ↑ Chaudhry IB, Husain N, Khan S, Badshah S, Deakin B, Kapur S (December 2007). "Amoxapine as an antipsychotic: comparative study versus haloperidol". Journal of Clinical Psychopharmacology. 27 (6): 575–581. doi:10.1097/jcp.0b013e31815a4424. PMID   18004123. S2CID   45880666.
  14. ↑ Sa DS, Kapur S, Lang AE (July–August 2001). "Amoxapine shows an antipsychotic effect but worsens motor function in patients with Parkinson's disease and psychosis". Clinical Neuropharmacology. 24 (4): 242–244. doi:10.1097/00002826-200107000-00010. PMID   11479398.
  15. ↑ Gelenberg AJ, Cooper DS, Doller JC, Maloof F (October 1979). "Galactorrhea and hyperprolactinemia associated with amoxapine therapy. Report of a case". JAMA. 242 (17): 1900–1901. doi:10.1001/jama.1979.03300170046029. PMID   573343.
  16. 1 2 "AMOXAPINE TABLET [WATSON LABORATORIES, INC.]". DailyMed. Watson Laboratories, Inc. July 2010. Retrieved 26 November 2013.
  17. ↑ "Side effects of antidepressant medications". UpToDate. Wolters Kluwer Health. Retrieved 26 November 2013.
  18. 1 2 Walker, R; Whittlesea, C, eds. (2007) [1994]. Clinical Pharmacy and Therapeutics (4th ed.). Edinburgh: Churchill Livingstone Elsevier. ISBN   978-0-7020-4293-5.
  19. ↑ White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology. 4 (4): 238–250. doi:10.1007/BF03161207. PMC   3550116 . PMID   19031375.
  20. ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  21. 1 2 3 4 Tatsumi M, Groshan K, Blakely RD, Richelson E (December 1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". European Journal of Pharmacology. 340 (2–3): 249–258. doi:10.1016/s0014-2999(97)01393-9. PMID   9537821.
  22. 1 2 3 4 Seeman P, Tallerico T (March 1998). "Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors". Molecular Psychiatry. 3 (2): 123–134. doi: 10.1038/sj.mp.4000336 . PMID   9577836.
  23. 1 2 3 4 5 Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ, Shen Y, et al. (March 1994). "Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors". The Journal of Pharmacology and Experimental Therapeutics. 268 (3): 1403–1410. PMID   7908055.
  24. ↑ Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, et al. (January 1996). "Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor". Journal of Neurochemistry. 66 (1): 47–56. doi:10.1046/j.1471-4159.1996.66010047.x. PMID   8522988. S2CID   35874409.
  25. 1 2 3 4 5 6 7 8 9 10 Richelson E, Nelson A (July 1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro". The Journal of Pharmacology and Experimental Therapeutics. 230 (1): 94–102. PMID   6086881.
  26. 1 2 3 Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, et al. (December 2005). "Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist". The Journal of Pharmacology and Experimental Therapeutics. 315 (3): 1278–1287. doi:10.1124/jpet.105.092155. PMID   16135699. S2CID   2247093.
  27. 1 2 3 Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (February 2012). "Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics". Naunyn-Schmiedeberg's Archives of Pharmacology. 385 (2): 145–170. doi:10.1007/s00210-011-0704-0. PMID   22033803. S2CID   253747520.
  28. 1 2 Pälvimäki EP, Roth BL, Majasuo H, Laakso A, Kuoppamäki M, Syvälahti E, Hietala J (August 1996). "Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor". Psychopharmacology. 126 (3): 234–240. doi:10.1007/BF02246453. PMID   8876023. S2CID   24889381.
  29. ↑ Glusa E, Pertz HH (June 2000). "Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT(2B) receptors". British Journal of Pharmacology. 130 (3): 692–698. doi:10.1038/sj.bjp.0703341. PMC   1572101 . PMID   10821800.
  30. 1 2 3 Gozlan H, Saddiki-Traki F, Merahi N, Laguzzi R, Hamon M (December 1991). "[Preclinical pharmacology of amoxapine and amitriptyline. Implications of serotoninergic and opiodergic systems in their central effect in rats]". L'Encéphale (in French). 17 Spec No 3: 415–422. PMID   1666997.
  31. 1 2 3 Wei HB, Niu XY (1990). "[Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration]". Yao Xue Xue Bao = Acta Pharmaceutica Sinica (in Chinese). 25 (12): 881–885. PMID   1966571.
  32. ↑ Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R (September 2005). "Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist". The Journal of Pharmacology and Experimental Therapeutics. 314 (3): 1310–1321. doi:10.1124/jpet.105.087965. PMID   15947036. S2CID   24248896.
  33. ↑ Sitte H, Freissmuth M (2 August 2006). Neurotransmitter Transporters. Springer Science & Business Media. pp. 472–. ISBN   978-3-540-29784-0.
  34. ↑ Onali P, Dedoni S, Olianas MC (January 2010). "Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes". The Journal of Pharmacology and Experimental Therapeutics. 332 (1): 255–265. doi:10.1124/jpet.109.159939. PMID   19828880. S2CID   18893305.
  35. ↑ Midha KK, Hubbard JW, McKay G, Rawson MJ, Hsia D (September 1999). "The role of metabolites in a bioequivalence study II: amoxapine, 7-hydroxyamoxapine, and 8-hydroxyamoxapine". International Journal of Clinical Pharmacology and Therapeutics. 37 (9): 428–438. PMID   10507241.
  36. 1 2 Jue SG, Dawson GW, Brogden RN (July 1982). "Amoxapine: a review of its pharmacology and efficacy in depressed states". Drugs. 24 (1): 1–23. doi:10.2165/00003495-198224010-00001. PMID   7049659. S2CID   7279867.
  37. ↑ Calvo B, García MJ, Pedraz JL, Mariño EL, Domínguez-Gil A (April 1985). "Pharmacokinetics of amoxapine and its active metabolites". International Journal of Clinical Pharmacology, Therapy, and Toxicology. 23 (4): 180–185. PMID   3997304.
  38. ↑ Takeuchi H, Yokota S, Shimada S, Ohtani Y, Miura S, Kubo H (April 1993). "Pharmacokinetics of amoxapine and its active metabolites in healthy subjects". Current Therapeutic Research. 53 (4): 427–434. doi:10.1016/S0011-393X(05)80202-4.
  39. ↑ "Amoxapine Monograph for Professionals - Drugs.com". Drugs.com. Bethesda, MD, USA: American Society of Health-System Pharmacists, Inc. 1 October 2007. Retrieved 30 November 2013.
  40. ↑ "Amoxapine -Drugs.com". Drugs.com. 2013. Retrieved 26 November 2013.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.