Asenapine: Difference between revisions

{{Short description|Medication to treat schizophrenia}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 457820862

| image = Asenapine Structural Formulae V.2.svg

| alt = Skeletal formula of asenapine

| width = 250px

| image2 = Asenapine-3D-balls.png

| alt2 = Ball-and-stick model of the asenapine molecule

| width2 = 225px

| tradename = Saphris, Sycrest, Secuado

| licence_EU = yes

| DailyMedID = Asenapine

| licence_US = Asenapine

| pregnancy_AU = C

| routes_of_administration = [[Sublingual administration|Sublingual]], [[Transdermal patch|transdermal]]

| class = [[Atypical antipsychotic]]

| ATC_prefix = N05

| ATC_suffix = AH05

| legal_AU = S4

| legal_BR = C1

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_UK = POM

| legal_UK_comment = <ref name = EMC />

| legal_US = Rx-only

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Sycrest EPAR">{{cite web | title=Sycrest EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/sycrest | access-date=9 September 2020}}</ref>

| bioavailability = 35% (sublingual), <2% (oral),<ref name = TGA>{{cite web|title=Product Information Saphris (asenapine maleate)|work=TGA eBusiness Services|publisher=Merck Sharp & Dohme (Australia) Pty Limited|date=14 January 2013|access-date=23 October 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03052-3|format=PDF}}</ref><ref name = DM>{{cite web|title=Saphris (asenapine maleate) tablet|work=DailyMed|publisher=Organon Pharmaceuticals|date=March 2013|access-date=23 October 2013|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=17209c32-56eb-4f84-954d-aed7b7a1b18d}}</ref><ref name = EMC>{{cite web | title=Sycrest 5mg sublingual tablets - Summary of Product Characteristics (SmPC) | website=(emc) | url=https://www.medicines.org.uk/emc/product/2807/smpc | access-date=9 September 2020}}</ref><ref name = EMA>{{cite web|title=Product information Sycrest – EMEA/H/C/001177 –II/0012|work=European Medicines Agency|publisher=N.V. Organon|date=21 February 2013|access-date=23 October 2013|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001177/WC500096895.pdf|archive-date=28 July 2017|archive-url=https://web.archive.org/web/20170728131424/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001177/WC500096895.pdf|url-status=dead}}</ref> transdermal bioavailability is significantly higher than sublingual<ref name="Carrithers 2020" /><ref name="suzuki-pk-2021">{{cite journal | vauthors = Suzuki K, Castelli M, Komaroff M, Starling B, Terahara T, Citrome L | title = Pharmacokinetic Profile of the Asenapine Transdermal System (HP-3070) | journal = Journal of Clinical Psychopharmacology | volume = 41 | issue = 3 | pages = 286–294 | date = 2021-03-16 | pmid = 33734167 | pmc = 8083160 | doi = 10.1097/JCP.0000000000001383 }}</ref>

| protein_bound = 95%<ref name = TGA/><ref name = DM/><ref name = EMC/><ref name = EMA/>

| metabolism = hepatic (glucurinodation by [[UGT1A4]] and oxidative metabolism by [[CYP1A2]])<ref name = TGA/><ref name = DM/><ref name = EMC/><ref name = EMA/>

| elimination_half-life = 24 hours (sublingual),<ref name = TGA/><ref name = DM/><ref name = EMC/><ref name = EMA/> 30 hours (transdermal),<ref name="Carrithers 2020" /> 33.9 hours (transdermal)<ref name="suzuki-pk-2021" />

| excretion = [[Kidney]] (50%), [[Faeces|Faecal]] (40%; ~5–16% as unchanged drug in faeces)<ref name = TGA/><ref name = DM/><ref name = EMC/><ref name = EMA/>

| index2_label = as salt

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 65576-45-6

| CAS_number2 = 85650-56-2

| PubChem = 163091

| PubChem2 = 6917875

| DrugBank = DB06216

| DrugBank2 = DBSALT000010

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID2 = 5293095

| UNII2 = CU9463U2E2

| KEGG = D11769

| KEGG2 = D02995

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 71253

| ChEBI2 = 71245

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1201756

| ChEMBL2 = 2040684

| synonyms = ORG-5222

<!--Chemical data-->

| IUPAC_name = (3a''RS'',12b''RS'')-''rel''-5-Chloro-2,3,3a,12b-tetrahydro-<br />2-methyl-1''H''-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole

| SMILES = Clc4cc2c(Oc1c(cccc1)[C@@H]3CN(C[C@@H]23)C)cc4

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI2 = 1S/C17H16ClNO.C4H4O4/c1-19-9-14-12-4-2-3-5-16(12)20-17-7-6-11(18)8-13(17)15(14)10-19;5-3(6)1-2-4(7)8/h2-8,14-15H,9-10H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-,15-;/m1./s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey2 = GMDCDXMAFMEDAG-CHHFXETESA-N

'''Asenapine''', sold under the brand name '''Saphris''' among others, is an [[atypical antipsychotic]] medication used to treat [[schizophrenia]] and acute [[mania]] associated with bipolar disorder as well as the medium to long-term management of [[bipolar disorder]].<ref name="Sycrest EPAR" /><ref name="pmid23719049" />

It was chemically derived via altering the chemical structure of the tetracyclic (''atypical'') antidepressant, [[mianserin]].<ref>{{cite journal | vauthors = Minassian A, Young JW | title = Evaluation of the clinical efficacy of asenapine in schizophrenia | journal = Expert Opinion on Pharmacotherapy | volume = 11 | issue = 12 | pages = 2107–2115 | date = August 2010 | pmid = 20642375 | pmc = 2924192 | doi = 10.1517/14656566.2010.506188 }}</ref>

It was initially approved in the United States in 2009<ref name="asenapinepi">{{cite web|url=http://www.spfiles.com/pisaphrisv1.pdf |title=Saphris (asenapine) prescribing information |access-date=2009-09-05 |date=2009-08-01 |publisher=Schering Corporation |archive-url=https://web.archive.org/web/20091122102620/http://www.spfiles.com/pisaphrisv1.pdf |archive-date=2009-11-22 |url-status=dead }}</ref> and approved as a [[generic medication]] in 2020.<ref>{{cite web | title=First Generic Drug Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | access-date=13 February 2021}}</ref>

== Medical uses ==

Asenapine has been approved by the FDA for the acute treatment of adults with [[schizophrenia]] and acute treatment of manic or mixed episodes associated with [[Bipolar disorder|bipolar I]] disorder with or without psychotic features in adults.<ref name="asenapinepi"></ref> In Australia asenapine's approved (and also listed on the [[Pharmaceutical Benefits Scheme|PBS]]) indications include the following:<ref>{{cite book | editor = Rossi, S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref>

* Schizophrenia

* Treatment, for up to 6 months, of an episode of acute mania or mixed episodes associated with [[Bipolar disorder|bipolar I disorder]]

* Maintenance treatment, as monotherapy, of bipolar I disorder

In the European Union and the United Kingdom, asenapine is only licensed for use as a treatment for acute mania in bipolar I disorder.<ref name = EMC/><ref name = EMA/><ref name="Sycrest EPAR" />

Asenapine is absorbed readily if administered [[sublingually]], asenapine is poorly absorbed when swallowed.<ref name="stoner 2012">{{cite journal | vauthors = Stoner SC, Pace HA | title = Asenapine: a clinical review of a second-generation antipsychotic | journal = Clinical Therapeutics | volume = 34 | issue = 5 | pages = 1023–1040 | date = May 2012 | pmid = 22494521 | doi = 10.1016/j.clinthera.2012.03.002 }}</ref> A [[transdermal patch|transdermal]] formulation of asenapine was approved in the United States in October 2019 under the brand name Secuado.<ref name="Carrithers 2020">{{cite journal | vauthors = Carrithers B, El-Mallakh RS | title = Transdermal Asenapine in Schizophrenia: A Systematic Review | journal = Patient Preference and Adherence | volume = 14 | pages = 1541–1551 | date = 18 March 2020 | pmid = 32943849 | pmc = 7468370 | doi = 10.2147/PPA.S235104 | doi-access = free }}</ref>

===Schizophrenia===

A [[Cochrane (organisation)|Cochrane]] [[systematic review]] found that while Asenapine has some preliminary evidence that it improves positive, negative, and depressive symptoms, it does not have enough research to merit a certain recommendation of asenapine for the treatment of schizophrenia.<ref name=Hay2015>{{cite journal | vauthors = Hay A, Byers A, Sereno M, Basra MK, Dutta S | title = Asenapine versus placebo for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 11 | pages = CD011458 | date = November 2015 | pmid = 26599405 | pmc = 6464872 | doi = 10.1002/14651858.CD011458.pub2 }}</ref>

===Bipolar disorder===

For the medium-term and long-term management and control of both depressive and manic features of bipolar disorder asenapine was found to be equally effective as olanzapine, but with a substantially superior side effect profile.<ref name="pmid23719049">{{cite journal | vauthors = Vita A, De Peri L, Siracusano A, Sacchetti E | title = Efficacy and tolerability of asenapine for acute mania in bipolar I disorder: meta-analyses of randomized-controlled trials | journal = International Clinical Psychopharmacology | volume = 28 | issue = 5 | pages = 219–227 | date = September 2013 | pmid = 23719049 | doi = 10.1097/YIC.0b013e32836290d2 | s2cid = 20871442 }}</ref>

In acute mania, asenapine was found to be significantly superior to placebo.<ref name="pmid23719049" /> As for its efficacy in the treatment of acute mania, a recent meta-analysis showed that it produces comparatively small improvements in manic symptoms in patients with acute mania and mixed episodes than most other antipsychotic drugs such as [[risperidone]] and [[olanzapine]] (with the exception of [[ziprasidone]]). Drop-out rates (in clinical trials) were also unusually high with asenapine.<ref name = LancetMa>{{cite journal | vauthors = Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, Purgato M, Spineli LM, Goodwin GM, Geddes JR | title = Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis | journal = Lancet | volume = 378 | issue = 9799 | pages = 1306–1315 | date = October 2011 | pmid = 21851976 | doi = 10.1016/S0140-6736(11)60873-8 | s2cid = 25512763 }}</ref> According to a [[post-hoc analysis]] of two 3-week clinical trials it may possess some antidepressant effects in patients with acute mania or mixed episodes.<ref>{{cite journal | vauthors = Szegedi A, Zhao J, van Willigenburg A, Nations KR, Mackle M, Panagides J | title = Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials | journal = BMC Psychiatry | volume = 11 | pages = 101 | date = June 2011 | pmid = 21689438 | pmc = 3152513 | doi = 10.1186/1471-244X-11-101 | doi-access = free }}</ref>

==Adverse effects==

'''<big>Adverse effect incidence</big>'''<ref name = TGA/><ref name = DM/><ref name = EMC/><ref name = EMA/>

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

* [[Somnolence]]

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

* Weight gain^{{dagger}}

* Increased appetite

* [[Extrapyramidal symptoms|Extrapyramidal side effects]] (EPS; such as [[dystonia]], [[akathisia]], [[dyskinesia]], muscle rigidity, [[parkinsonism]])

* Sedation

* Dizziness

* [[Dysgeusia]] (altered taste)

* Oral [[hypoaesthesia]] (numbness), only when taken sublingually. Transdermal asenapine was shown to eliminate this side effect.<ref name="Carrithers 2020" />

* Increased [[alanine aminotransferase]]

* Dyspepsia, stomach discomfort, and/or vomiting{{efn|The Phase III trials used for FDA approval in the US used lists of "elicited side effects", asking all subjects about each side effect on the list, and "nausea" was not included. The elicited side effects list included the related symptoms of "dyspepsia", "stomach discomfort", and "vomiting", and the incidence of each was higher than placebo and in the range of 1 to 10% of asenapine-treated subjects.<ref name=DM />}}

* Fatigue

'''Uncommon (0.1–1% incidence) adverse effects include:'''

* [[Hyperglycaemia]] — elevated blood glucose (sugar)

* [[Syncope (medicine)|Syncope]]

* Seizure

* [[Dysarthria]]

* [[sinus bradycardia]]

* [[Bundle branch block]]

* [[QT interval|QTc interval prolongation]] (has a relatively low risk for causing QTc interval prolongation.<ref>{{cite journal| vauthors = Washington NB, Brahm NC, Kissack J |title=Which psychotropics carry the greatest risk of QTc prolongation?|journal=Current Psychiatry |date=October 2012 |volume=11 |issue=10 |pages=36–39 |url= http://www.mdedge.com/currentpsychiatry/article/64870/anxiety-disorders/which-psychotropics-carry-greatest-risk-qtc |access-date=14 April 2017}}</ref><ref name="Maudsley">{{cite book | isbn = 978-0-470-97948-8 | title = The Maudsley prescribing guidelines in psychiatry | vauthors = Taylor D, Paton C, Shitij K | year = 2012 | publisher = Wiley-Blackwell | location = West Sussex }}</ref>)

* [[sinus tachycardia]]

* Orthostatic hypotension

* [[Hypotension]]

* Swollen tongue

* [[Dysphagia]] (difficulty swallowing)

* [[Glossodynia]]

* Oral [[paraesthesia]]

'''Rare (0.01–0.1% incidence) adverse effects include:'''

* [[Neuroleptic malignant syndrome]] (Combination of [[fever]], muscle stiffness, [[Hyperventilation|faster breathing]], [[sweating]], reduced consciousness, and sudden change in [[blood pressure]] and [[heart rate]])

* [[Tardive dyskinesia]]

* Speech disturbance

* [[Rhabdomyolysis]]

* [[Angioedema]]

* Blood dyscrasias such as [[agranulocytosis]], [[leukopenia]] and [[neutropenia]]

* Accommodation disorder{{clarify|date=February 2016}}

* [[Pulmonary embolism]]

* [[Gynaecomastia]]

* [[Galactorrhoea]]

'''Unknown incidence adverse effects'''

* Allergic reaction

* Restless legs syndrome

* Oral mucosal lesions (ulcerations, blistering and inflammation)

* Salivary hypersecretion

* [[Hyperprolactinaemia]]

^{{dagger}} Asenapine seems to have a relatively low weight gain liability for an [[atypical antipsychotic]] (which are notorious for their metabolic side effects) and a 2013 meta-analysis found ''[[statistical significance|significantly]]'' less weight gain (SMD [standard mean difference in weight gained in those on placebo vs. active drug]: 0.23; [[Confidence interval|95% CI]]: 0.07-0.39) than, [[paliperidone]] (SMD: 0.38; 95% CI: 0.27-0.48), [[risperidone]] (SMD: 0.42; 95% CI: 0.33-0.50), [[quetiapine]] (SMD: 0.43; 95% CI: 0.34-0.53), [[sertindole]] (SMD: 0.53; 95% CI: 0.38-0.68), [[chlorpromazine]] (SMD: 0.55; 95% CI: 0.34-0.76), [[iloperidone]] (SMD: 0.62; 95% CI: 0.49-0.74), [[clozapine]] (SMD: 0.65; 95% CI: 0.31-0.99), [[zotepine]] (SMD: 0.71; 95% CI: 0.47-0.96) and [[olanzapine]] (SMD: 0.74; 95% CI: 0.67-0.81) and ''approximately'' (that is, no statistically significant difference at the [[Hypothesis testing|p=0.05]] level) as much as weight gain as [[aripiprazole]] (SMD: 0.17; 95% CI: 0.05-0.28), [[lurasidone]] (SMD: 0.10; 95% CI: –0.02-0.21), [[amisulpride]] (SMD: 0.20; 95% CI: 0.05-0.35), [[haloperidol]] (SMD: 0.09; 95% CI: 0.00-0.17) and [[ziprasidone]] (SMD: 0.10; 95% CI: –0.02-0.22).<ref name=Lancet/> Its potential for elevating plasma prolactin levels seems relatively limited too according to this meta-analysis.<ref name=Lancet/> This meta-analysis also found that asenapine has approximately the same odds ratio (3.28; 95% CI: 1.37-6.69) for causing sedation [compared to placebo-treated patients] as [[olanzapine]] (3.34; 95% CI: 2.46-4.50]) and [[haloperidol]] (2.76; 95% CI: 2.04-3.66) and a higher odds ratio (although not ''significantly'') for sedation than [[aripiprazole]] (1.84; 95% CI: 1.05-3.05), [[paliperidone]] (1.40; 95% CI: 0.85-2.19) and [[amisulpride]] (1.42; 95% CI: 0.72 to 2.51) to name a few and is hence a mild-moderately sedating antipsychotic.<ref name=Lancet>{{cite journal | vauthors = Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}</ref> The same meta-analysis suggested that asenapine had a relatively high risk of extrapyramidal symptoms compared to other atypical antipsychotics but a lower risk than first-generation or [[Typical antipsychotic|typical antipsychotics]].<ref name=Lancet/>

===Discontinuation===

For all antipsychotics, the [[British National Formulary]] recommends a gradual dose reduction when discontinuing to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">{{cite book |editor1-first=BMJ | editor = Joint Formulary Committee | title = British National Formulary | edition = 57 | date = March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=978-0-85369-845-6 |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}}</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>{{cite book | vauthors = Haddad P, Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=9780198527480 |pages=207–216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |language=en}}</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004/> Symptoms generally resolve after a short period of time.<ref name=Had2004/>

There is tentative evidence that discontinuation of antipsychotics can result in psychosis as a transient withdrawal symptom.<ref>{{cite journal | vauthors = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatrica Scandinavica | volume = 114 | issue = 1 | pages = 3–13 | date = July 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x | s2cid = 6267180 }}</ref> It may also result in recurrence of the condition that is being treated.<ref>{{cite book | vauthors = Sacchetti E, Vita A, Siracusano A, Fleischhacker W |title=Adherence to Antipsychotics in Schizophrenia |date=2013 |publisher=Springer Science & Business Media |isbn=9788847026797 |page=85 |url=https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |language=en}}</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/>

==Pharmacology==

===Pharmacodynamics===

{{See also|Atypical antipsychotic#Pharmacodynamics|Antipsychotic#Comparison of medications}}

{| class="wikitable floatright sortable" style="font-size:small;"

|+ Asenapine<ref name="pmid18308814"/><ref name="asenapinepi"/>

! Site !! pK_i !! K_i (nM) || Action

| [[5-HT1A receptor|5-HT_1A]] || 8.6 || 2.5 || Partial agonist

| [[5-HT1B receptor|5-HT_1B]] || 8.4 || 4.0 || Antagonist

| [[5-HT2A receptor|5-HT_2A]] || 10.2 || 0.06 || Antagonist

| [[5-HT2B receptor|5-HT_2B]] || 9.8 || 0.16 || Antagonist

| [[5-HT2C receptor|5-HT_2C]] || 10.5 || 0.03 || Antagonist

| [[5-HT5A receptor|5-HT_5A]] || 8.8 || 1.6 || Antagonist

| [[5-HT6 receptor|5-HT₆]] || 9.5 || 0.25 || Antagonist

| [[5-HT7 receptor|5-HT₇]] || 9.9 || 0.13 || Antagonist

| [[alpha-1 adrenergic receptor|α₁]] || 8.9 || 1.2 || Antagonist

| [[alpha-2A adrenergic receptor|α_2A]] || 8.9 || 1.2 || Antagonist

| [[alpha-2B adrenergic receptor|α_2B]] || 9.5 || 0.32 || Antagonist

| [[alpha-2C adrenergic receptor|α_2C]] || 8.9 || 1.2 || Antagonist

| [[D1 receptor|D₁]] || 8.9 || 1.4 || Antagonist

| [[D2 receptor|D₂]] || 8.9 || 1.3 || Antagonist

| [[D3 receptor|D₃]] || 9.4 || 0.42 || Antagonist

| [[D4 receptor|D₄]] || 9.0 || 1.1 || Antagonist

| [[H1 receptor|H₁]] || 9.0 || 1.0 || Antagonist

| [[H2 receptor|H₂]] || 8.2 || 6.2 || Antagonist

| [[Muscarinic acetylcholine receptor|mACh]] || <5 || 8128 || Antagonist

Asenapine shows high [[Affinity (pharmacology)|affinity]] (pKi) for numerous [[Receptor (biochemistry)|receptors]], including the [[serotonin]] [[5-HT1A|5-HT_1A]] (8.6), [[5-HT1B|5-HT_1B]] (8.4), [[5-HT2A|5-HT_2A]] (10.2), [[5-HT2B receptor|5-HT_2B]] (9.8), [[5-HT2C|5-HT_2C]] (10.5), [[5-HT5A|5-HT_5A]] (8.8), [[5-HT6|5-HT₆]] (9.5), and [[5-HT7|5-HT₇]] (9.9) receptors, the [[adrenaline|adrenergic]] [[Alpha-1 adrenergic receptor|α₁]] (8.9), [[Alpha-2A adrenergic receptor|α_2A]] (8.9), [[Alpha-2B adrenergic receptor|α_2B]] (9.5), and [[Alpha-2C adrenergic receptor|α_2C]] (8.9) receptors, the [[dopamine]] [[Dopamine receptor D1|D₁]] (8.9), [[Dopamine receptor D2|D₂]] (8.9), [[Dopamine receptor D3|D₃]] (9.4), and [[Dopamine receptor D4|D₄]] (9.0) receptors, and the [[histamine]] [[Histamine H1 receptor|H₁]] (9.0) and [[Histamine H2 receptor|H₂]] (8.2) receptors. It has much lower affinity (pKi < 5) for the [[muscarinic acetylcholine receptor]]s. Asenapine behaves as a partial [[agonist]] at the 5-HT_1A receptors.<ref>{{cite journal | vauthors = Ghanbari R, El Mansari M, Shahid M, Blier P | title = Electrophysiological characterization of the effects of asenapine at 5-HT(1A), 5-HT(2A), alpha(2)-adrenergic and D(2) receptors in the rat brain | journal = European Neuropsychopharmacology | volume = 19 | issue = 3 | pages = 177–187 | date = March 2009 | pmid = 19116183 | doi = 10.1016/j.euroneuro.2008.11.001 | s2cid = 140204044 }}</ref> At all other targets asenapine is an [[receptor antagonist|antagonist]].<ref name="pmid18308814">{{cite journal | vauthors = Shahid M, Walker GB, Zorn SH, Wong EH | title = Asenapine: a novel psychopharmacologic agent with a unique human receptor signature | journal = Journal of Psychopharmacology | volume = 23 | issue = 1 | pages = 65–73 | date = January 2009 | pmid = 18308814 | doi = 10.1177/0269881107082944 | s2cid = 206489515 }}</ref>

Even relative to other atypical antipsychotics, asenapine has unusually high affinity for the [[5-HT2A|5-HT_2A]], [[5-HT2C|5-HT_2C]], [[5-HT6|5-HT₆]], and [[5-HT7|5-HT₇]] receptors, and very high affinity for the [[Alpha 2 receptor|α₂]] and [[H1 receptor|H₁]] receptors.<ref name="pmid18308814"/>

{{clear}}

==Notes==

{{notelist}}

{{Reflist}}

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/asenapine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Asenapine }}

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/asenapine%20maleate | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Asenapine maleate }}

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{{Portal bar | Medicine}}

[[Category:5-HT1A agonists]]

[[Category:Drugs developed by AbbVie]]

[[Category:Alpha-2 blockers]]

[[Category:Chloroarenes]]

[[Category:Heterocyclic compounds with 4 rings]]

[[Category:Drugs developed by Merck & Co.]]

[[Category:Nitrogen heterocycles]]

[[Category:Oxygen heterocycles]]

[[Category:Drugs developed by Schering-Plough]]

[[Category:Tertiary amines]]