Asenapine

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Asenapine
Asenapine Structural Formulae V.2.svg
Asenapine-3D-balls.png
Clinical data
Trade names Saphris, Sycrest, Secuado
Other namesORG-5222
AHFS/Drugs.com Monograph
MedlinePlus a610015
License data
Pregnancy
category
  • AU:C
Routes of
administration 		Sublingual, transdermal
Drug class Atypical antipsychotic
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 35% (sublingual), <2% (oral), [5] [6] [2] [7] transdermal bioavailability is significantly higher than sublingual [8] [9]
Protein binding 95% [5] [6] [2] [7]
Metabolism hepatic (glucurinodation by UGT1A4 and oxidative metabolism by CYP1A2) [5] [6] [2] [7]
Elimination half-life 24 hours (sublingual), [5] [6] [2] [7] 30 hours (transdermal), [8] 33.9 hours (transdermal) [9]
Excretion Kidney (50%), Faecal (40%; ~5–16% as unchanged drug in faeces) [5] [6] [2] [7]
Identifiers
  • (3aRS,12bRS)-rel-5-Chloro-2,3,3a,12b-tetrahydro-
    2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.059.828 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H16ClNO
Molar mass 285.77 g·mol−1
3D model (JSmol)
  • Clc4cc2c(Oc1c(cccc1)[C@@H]3CN(C[C@@H]23)C)cc4
  • InChI=1S/C17H16ClNO/c1-19-9-14-12-4-2-3-5-16(12)20-17-7-6-11(18)8-13(17)15(14)10-19/h2-8,14-15H,9-10H2,1H3/t14-,15-/m0/s1 Yes check.svgY
  • Key:VSWBSWWIRNCQIJ-GJZGRUSLSA-N Yes check.svgY

  • as salt: InChI=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
  • Key:GMDCDXMAFMEDAG-CHHFXETESA-N
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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. [4] [10]

Contents

It was chemically derived via altering the chemical structure of the tetracyclic (atypical) antidepressant, mianserin. [11]

It was initially approved in the United States in 2009 [12] and approved as a generic medication in 2020. [13]

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 I disorder with or without psychotic features in adults. [12] In Australia asenapine's approved (and also listed on the PBS) indications include the following: [14]

In the European Union and the United Kingdom, asenapine is only licensed for use as a treatment for acute mania in bipolar I disorder. [2] [7] [4]

Asenapine is absorbed readily if administered sublingually, asenapine is poorly absorbed when swallowed. [15] A transdermal formulation of asenapine was approved in the United States in October 2019 under the brand name Secuado. [8]

Schizophrenia

A 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. [16]

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. [10]

In acute mania, asenapine was found to be significantly superior to placebo. [10] 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. [17] 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. [18]

Adverse effects

Adverse effect incidence [5] [6] [2] [7]

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

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

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

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

Unknown incidence adverse effects

† 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 significantly less weight gain (SMD [standard mean difference in weight gained in those on placebo vs. active drug]: 0.23; 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 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). [21] Its potential for elevating plasma prolactin levels seems relatively limited too according to this meta-analysis. [21] 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. [21] 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 antipsychotics. [21]

Discontinuation

For all antipsychotics, the British National Formulary recommends a gradual dose reduction when discontinuing to avoid acute withdrawal syndrome or rapid relapse. [22] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. [23] Other symptoms may include restlessness, increased sweating, and trouble sleeping. [23] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. [23] Symptoms generally resolve after a short period of time. [23]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis as a transient withdrawal symptom. [24] It may also result in recurrence of the condition that is being treated. [25] Rarely tardive dyskinesia can occur when the medication is stopped. [23]

Pharmacology

Pharmacodynamics

Asenapine [26] [12]
SitepKiKi (nM)Action
5-HT1A 8.62.5Partial agonist
5-HT1B 8.44.0Antagonist
5-HT2A 10.20.06Antagonist
5-HT2B 9.80.16Antagonist
5-HT2C 10.50.03Antagonist
5-HT5A 8.81.6Antagonist
5-HT6 9.50.25Antagonist
5-HT7 9.90.13Antagonist
α1 8.91.2Antagonist
α2A 8.91.2Antagonist
α2B 9.50.32Antagonist
α2C 8.91.2Antagonist
D1 8.91.4Antagonist
D2 8.91.3Antagonist
D3 9.40.42Antagonist
D4 9.01.1Antagonist
H1 9.01.0Antagonist
H2 8.26.2Antagonist
mACh <58128Antagonist

Asenapine shows high affinity (pKi) for numerous receptors, including the serotonin 5-HT1A (8.6), 5-HT1B (8.4), 5-HT2A (10.2), 5-HT2B (9.8), 5-HT2C (10.5), 5-HT5A (8.8), 5-HT6 (9.5), and 5-HT7 (9.9) receptors, the adrenergic α1 (8.9), α2A (8.9), α2B (9.5), and α2C (8.9) receptors, the dopamine D1 (8.9), D2 (8.9), D3 (9.4), and D4 (9.0) receptors, and the histamine H1 (9.0) and H2 (8.2) receptors. It has much lower affinity (pKi < 5) for the muscarinic acetylcholine receptors. Asenapine behaves as a partial agonist at the 5-HT1A receptors. [27] At all other targets asenapine is an antagonist. [26]

Even relative to other atypical antipsychotics, asenapine has unusually high affinity for the 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors, and very high affinity for the α2 and H1 receptors. [26]

Notes

  1. ↑ 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. [6]

Related Research Articles

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

Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.

<span class="mw-page-title-main">Mood stabilizer</span> Psychiatric medication used to treat mood disorders

A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder.

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

Clozapine is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is primarily used to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to two other antipsychotics, or who have been unable to tolerate other drugs due to extrapyramidal side effects. It is also used for the treatment of psychosis in Parkinson's disease.

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

Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

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

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

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

Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.

<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 may not outweigh its undesirable side effects. It is taken orally.

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

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.

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

Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

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

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.

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

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder; other uses include as an add-on treatment in major depressive disorder and obsessive compulsive disorder (OCD), tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

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

Sertindole, sold under the brand name Serdolect among others, is an antipsychotic medication. Sertindole was developed by the Danish pharmaceutical company Lundbeck and marketed under license by Abbott Labs. Like other atypical antipsychotics, it has activity at dopamine and serotonin receptors in the brain. It is used in the treatment of schizophrenia. It is classified chemically as a phenylindole derivative.

<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">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

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

Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia.

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

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.

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

Lurasidone, sold under the brand name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.

<span class="mw-page-title-main">Cariprazine</span> Atypical antipsychotic medicine

Cariprazine, sold under the brand name Vraylar among others, is an atypical antipsychotic developed by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, bipolar depression, and major depressive disorder. It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors, with high selectivity for the D3 receptor. It is taken by mouth.

Antimanic drugs are psychotropic drugs that are used to treat symptoms of mania. Though there are different causes of mania, the majority is caused by bipolar disorder, therefore antimanic drugs are mostly similar to drugs treating bipolar disorder. Since 1970s, antimanic drugs have been used specifically to control the abnormal elevation of mood or mood swings during manic episodes. One purpose of antimanic drugs is to alleviate or shorten the duration of an acute mania. Another objective is to prevent further cycles of mania and maintain the improvement achieved during the acute episode. The mechanism of antimanic drugs has not yet been fully known, it is proposed that they mostly affect chemical neurotransmitters in the brain. However, the usage of antimanic drugs should be consulted with a doctor or pharmacist due to their side effects and interactions with other drugs and food.

References

  1. ↑ Anvisa (2023-03-31). "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 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. 1 2 3 4 5 6 7 8 "Sycrest 5mg sublingual tablets - Summary of Product Characteristics (SmPC)". (emc). Retrieved 9 September 2020.
  3. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  4. 1 2 3 "Sycrest EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 9 September 2020.
  5. 1 2 3 4 5 6 "Product Information Saphris (asenapine maleate)" (PDF). TGA eBusiness Services. Merck Sharp & Dohme (Australia) Pty Limited. 14 January 2013. Retrieved 23 October 2013.
  6. 1 2 3 4 5 6 7 "Saphris (asenapine maleate) tablet". DailyMed. Organon Pharmaceuticals. March 2013. Retrieved 23 October 2013.
  7. 1 2 3 4 5 6 7 "Product information Sycrest – EMEA/H/C/001177 –II/0012" (PDF). European Medicines Agency. N.V. Organon. 21 February 2013. Archived from the original (PDF) on 28 July 2017. Retrieved 23 October 2013.
  8. 1 2 3 4 Carrithers B, El-Mallakh RS (18 March 2020). "Transdermal Asenapine in Schizophrenia: A Systematic Review". Patient Preference and Adherence. 14: 1541–1551. doi: 10.2147/PPA.S235104 . PMC   7468370 . PMID   32943849.
  9. 1 2 Suzuki K, Castelli M, Komaroff M, Starling B, Terahara T, Citrome L (2021-03-16). "Pharmacokinetic Profile of the Asenapine Transdermal System (HP-3070)". Journal of Clinical Psychopharmacology. 41 (3): 286–294. doi:10.1097/JCP.0000000000001383. PMC   8083160 . PMID   33734167.
  10. 1 2 3 Vita A, De Peri L, Siracusano A, Sacchetti E (September 2013). "Efficacy and tolerability of asenapine for acute mania in bipolar I disorder: meta-analyses of randomized-controlled trials". International Clinical Psychopharmacology. 28 (5): 219–227. doi:10.1097/YIC.0b013e32836290d2. PMID   23719049. S2CID   20871442.
  11. ↑ Minassian A, Young JW (August 2010). "Evaluation of the clinical efficacy of asenapine in schizophrenia". Expert Opinion on Pharmacotherapy. 11 (12): 2107–2115. doi:10.1517/14656566.2010.506188. PMC   2924192 . PMID   20642375.
  12. 1 2 3 "Saphris (asenapine) prescribing information" (PDF). Schering Corporation. 2009-08-01. Archived from the original (PDF) on 2009-11-22. Retrieved 2009-09-05.
  13. ↑ "First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). Retrieved 13 February 2021.
  14. ↑ Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN   978-0-9805790-9-3.
  15. ↑ Stoner SC, Pace HA (May 2012). "Asenapine: a clinical review of a second-generation antipsychotic". Clinical Therapeutics. 34 (5): 1023–1040. doi:10.1016/j.clinthera.2012.03.002. PMID   22494521.
  16. ↑ Hay A, Byers A, Sereno M, Basra MK, Dutta S (November 2015). "Asenapine versus placebo for schizophrenia". The Cochrane Database of Systematic Reviews. 2015 (11): CD011458. doi:10.1002/14651858.CD011458.pub2. PMC   6464872 . PMID   26599405.
  17. ↑ Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, et al. (October 2011). "Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis". Lancet. 378 (9799): 1306–1315. doi:10.1016/S0140-6736(11)60873-8. PMID   21851976. S2CID   25512763.
  18. ↑ Szegedi A, Zhao J, van Willigenburg A, Nations KR, Mackle M, Panagides J (June 2011). "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". BMC Psychiatry. 11: 101. doi: 10.1186/1471-244X-11-101 . PMC   3152513 . PMID   21689438.
  19. ↑ Washington NB, Brahm NC, Kissack J (October 2012). "Which psychotropics carry the greatest risk of QTc prolongation?". Current Psychiatry. 11 (10): 36–39. Retrieved 14 April 2017.
  20. ↑ Taylor D, Paton C, Shitij K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN   978-0-470-97948-8.
  21. 1 2 3 4 Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. PMID   23810019. S2CID   32085212.
  22. ↑ Joint Formulary Committee B, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN   978-0-85369-845-6. 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.
  23. 1 2 3 4 5 Haddad P, Haddad PM, Dursun S, Deakin B (2004). Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. pp. 207–216. ISBN   9780198527480.
  24. ↑ Moncrieff J (July 2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatrica Scandinavica. 114 (1): 3–13. doi:10.1111/j.1600-0447.2006.00787.x. PMID   16774655. S2CID   6267180.
  25. ↑ Sacchetti E, Vita A, Siracusano A, Fleischhacker W (2013). Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. p. 85. ISBN   9788847026797.
  26. 1 2 3 Shahid M, Walker GB, Zorn SH, Wong EH (January 2009). "Asenapine: a novel psychopharmacologic agent with a unique human receptor signature". Journal of Psychopharmacology. 23 (1): 65–73. doi:10.1177/0269881107082944. PMID   18308814. S2CID   206489515.
  27. ↑ Ghanbari R, El Mansari M, Shahid M, Blier P (March 2009). "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". European Neuropsychopharmacology. 19 (3): 177–187. doi:10.1016/j.euroneuro.2008.11.001. PMID   19116183. S2CID   140204044.
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