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Amoxapine

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Amoxapine
Systematic (IUPAC) name
2-chloro-11-(piperazin-1-yl)dibenzo[b,f][1,4]oxazepine
Clinical data
Trade names Asendin
AHFS/Drugs.com monograph
MedlinePlus a682202
Pregnancy cat. C(US)
Legal status ℞-only (US)
Routes Oral
Pharmacokinetic data
Bioavailability  ?
Protein binding 90%[1]
Metabolism Hepatic (cytochrome P450 system)
Half-life 8-10 hours (30 hours for major metabolites)[1]
Excretion Renal
Identifiers
CAS number 14028-44-5 YesY
ATC code N06AA17
PubChem CID 2170
IUPHAR ligand 201
DrugBank APRD00142
ChemSpider 2085 YesY
UNII R63VQ857OT YesY
KEGG D00228 YesY
ChEBI CHEBI:2675 YesY
ChEMBL CHEMBL1113 YesY
Chemical data
Formula C17H16ClN3O 
Mol. mass 313.781 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Amoxapine (Amokisan, Asendin, Asendis, Defanyl, Demolox, Moxadil) is a tetracyclic antidepressant of the dibenzoxazepine family, though it is often classified as a secondary amine tricyclic antidepressant.

Contents

[edit] Uses

Amoxapine is used in the treatment of depression, anxiety disorders, panic disorder, and bipolar disorder. It also has properties similar to those of atypical antipsychotic,[2][3] and may be used in the treatment of schizophrenic psychosis off-label.

[edit] Pharmacology

Amoxapine possesses a wide array of pharmacological effects. It is a moderate and strong reuptake inhibitor of serotonin and norepinephrine, respectively,[4] and binds to the 5-HT2A,[5] 5-HT2B,[6] 5-HT2C,[5] 5-HT3,[7] 5-HT6,[8] 5-HT7,[8] D2,[9] α1-adrenergic,[9] D3[10], D4,[10] and H1 receptors[9] 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,[7] 5-HT1B,[7] D1,[11] α2-adrenergic,[9] H4,[12] mACh,[9] and GABAA receptors,[11] and no affinity for the β-adrenergic receptors or the allosteric benzodiazepine site on the GABAA receptor.[11]

7-Hydroxyamoxapine, a major active metabolite of amoxapine, is a more potent dopamine receptor antagonist and contributes to its neuroleptic efficacy,[2] 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.[13]

[edit] Side effects

Common side effects of amoxapine include hypotension, drowsiness, dry mouth, constipation, blurred vision, fatigue, and vertigo.[1] Additionally, due to the drug's and its metabolite 7-hyroxyamoxapine's potent blockade of dopamine receptors, it can cause neuroleptic malignant syndrome as well as acute extrapyramidal symptoms and tardive dyskinesia. Cardiovascular and anticholinergic side effects are much reduced compared to other tri- and tetracyclic antidepressants.

[edit] Contraindications

The drug is contraindicated in children because it lowers the seizure threshold to the extent that fits may be precipitated.[citation needed]

[edit] See also

[edit] References

  1. ^ a b c Kinney JL, Evans RL (1982). "Evaluation of amoxapine". Clinical Pharmacy 1 (5): 417–24. PMID 6764165. 
  2. ^ 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): 1165–7. PMID 6126130. http://ajp.psychiatryonline.org/article.aspx?volume=139&page=1165. 
  3. ^ Apiquian R, Fresan A, Ulloa RE, 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. 
  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): 249–58. doi:10.1016/S0014-2999(97)01393-9. PMID 9537821. http://linkinghub.elsevier.com/retrieve/pii/S0014-2999(97)01393-9. 
  5. ^ a b Pälvimäki EP, Roth BL, Majasuo H, et al. (August 1996). "Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor". Psychopharmacology 126 (3): 234–40. doi:10.1007/BF02246453. PMID 8876023. http://link.springer.de/link/service/journals/00213/bibs/6126003/61260234.htm. 
  6. ^ Glusa E, Pertz HH (June 2000). "Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT2B receptors". British Journal of Pharmacology 130 (3): 692–8. doi:10.1038/sj.bjp.0703341. PMC 1572101. PMID 10821800. http://dx.doi.org/10.1038/sj.bjp.0703341. 
  7. ^ a b c 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]" (in French). L'Encéphale 17 Spec No 3: 415–22. PMID 1666997. 
  8. ^ a b Roth BL, Craigo SC, Choudhary MS, 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): 1403–10. PMID 7908055. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7908055. 
  9. ^ a b c d e 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. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6086881. 
  10. ^ a b Burstein ES, Ma J, Wong S, 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): 1278–87. doi:10.1124/jpet.105.092155. PMID 16135699. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16135699. 
  11. ^ a b c 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]" (in Chinese). Yao Xue Xue Bao = Acta Pharmaceutica Sinica 25 (12): 881–5. PMID 1966571. 
  12. ^ 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): 1310–21. doi:10.1124/jpet.105.087965. PMID 15947036. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15947036. 
  13. ^ 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): 428–38. PMID 10507241. 
GABAA PAMs
Others
α2δ VDCC Blockers
5-HT1A Agonists
Azapirones: Buspirone • Gepirone • Tandospirone; Others: Flesinoxan • Oxaflozane
H1 Antagonists
Diphenylmethanes: Captodiame • Hydroxyzine; Others: Brompheniramine • Chlorpheniramine • Pheniramine
CRH1 Antagonists
NK2 Antagonists
MCH1 antagonists
mGluR2/3 Agonists
mGluR5 NAMs
TSPO agonists
σ1 agonists
Others

M: PSO/PSI

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc(eval/thrp), drug(N5A/5B/5C/6A/6B/6D)
Antipsychotics (neuroleptics) (N05A)
Typical
Benzamides: Levosulpiride • Nemonapride • Sulpiride • Sultopride • Tiapride • Veralipride; Butyrophenones: Azaperone • Benperidol • Bromperidol • Droperidol • Fluanisone • Haloperidol • Lenperone • Moperone • Pipamperone • Spiperone • Timiperone • Trifluperidol; Diphenylbutylpiperidines: Clopimozide • Fluspirilene • Penfluridol • Pimozide; Phenothiazines: Acepromazine • Acetophenazine • Butaperazine • Carphenazine • Chloracizine • Chlorproethazine • Chlorpromazine • Cyamemazine • Dixyrazine • Fluacizine • Fluphenazine • Levomepromazine/Methotrimeprazine • Mesoridazine • Perazine • Pericyazine • Perphenazine • Piperacetazine • Pipotiazine • Prochlorperazine • Promazine • Promethazine • Propiomazine • Sulforidazine • Thiethylperazine • Thiopropazate • Thioproperazine • Thioridazine • Trifluoperazine • Triflupromazine; Thioxanthenes: Chlorprothixene • Clopenthixol • Flupentixol • Thiothixene • Zuclopenthixol; Tricyclics: Amoxapine • Butaclamol • Fluotracen • Loxapine • Trimipramine; Others: Prothipendyl
Atypical
Others

M: PSO/PSI

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc(eval/thrp), drug(N5A/5B/5C/6A/6B/6D)
Classes
Antidepressants
Antihistamines
Antipsychotics
Others
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