MedKoo Cat#: 326708 | Name: Asenapine maleate

MedKoo Cat#: 326708

Name: Asenapine maleate

CAS#: 85650-56-2 (maleate)

Chemical Formula: C21H20ClNO5

Exact Mass: 0.0000

Molecular Weight: 401.84

Elemental Analysis: C, 62.77; H, 5.02; Cl, 8.82; N, 3.49; O, 19.91

Related CAS #:85650-56-2 (maleate) 65576-45-6 (free)

Synonym:Org 5222; Org5222; Org-5222; HSDB 8061; HSDB-8061; HSDB8061; Asenapine; Asenapine maleate; trade names Saphris and Sycrest.

IUPAC/Chemical Name:(3aS,12bS)-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrole maleate

InChi Key:GMDCDXMAFMEDAG-CHHFXETESA-N

InChi Code: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

SMILES Code:CN1C[C@@](C2=CC=CC=C2OC3=CC=C(Cl)C=C34)([H])[C@]4([H])C1.O=C(O)/C=C\C(O)=O

Appearance:Solid powder

Purity:>98% (or refer to the Certificate of Analysis)

Shipping Condition:Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:Soluble in DMSO, not in water

Shelf Life:>2 years if stored properly

Drug Formulation:This drug may be formulated in DMSO

Stock Solution Storage:0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code:2934.99.9001

More Info Related:

85650-56-2 ( Asenapine maleate)

65576-45-6 ( Asenapine free)

1412458-61-7 ( Asenapine HCl).

Biological target:Asenapine maleate is a 5-HT (1A, 1B, 2A, 2B, 2C, 5A, 6, 7) and D2 antagonist with Ki values of 0.03-4.0 nM, 1.3nM, respectively, and an antipsychotic.

In vitro activity:To further determine whether AM (Asenapine maleate) act through ROS mediated signaling pathway, CFs were pretreated with or without AM followed by Ang II stimulation. The results demonstrated that AM could reduce the levels of ROS induced by Ang II (Fig. 4A). After pretreatment with 10 μM AM, the Ang II-induced activation of the TGFβ1/MAPK signal pathway was suppressed. Treatment with AM also reduced the expression of TGFβ1 and decreased the phosphorylation levels of ERK, JNK, and p38MAPK. Therefore, this study confirmed that AM can inhibit Ang II-induced cardiac fibrosis through the ROS/TGFβ1/MAPK signaling pathway (Fig. 4B and C).

Reference: Biochem Biophys Res Commun. 2021 May 14;553:172-179. https://pubmed.ncbi.nlm.nih.gov/33773140/

In vivo activity:As expected, administration of cumulative doses of the 5‐HT7 agonist LP‐44 (1‐4 mg/kg, i.v.) in control rats induced a dose‐dependent decrease in the firing activity of DR 5‐HT neurons with ED50=1.45 mg/kg (n=7; Figure 3A,B). Two‐way repeated‐measures ANOVA revealed a significant effect of SB 269970 pretreatment (F1,40=6.98, P<.05) on the potency of LP‐44 (F4,40=54.13, P<.001), but no SB 269970 x LP‐44 interaction. Similarly, an injection of Asenapine (1 mg/kg, i.v.) reduced the suppressant effect of LP‐44 on the firing activity of DR 5‐HT neurons, with ED50=3.54 mg/kg (n=7, Figure 3C,D). Two‐way repeated‐measures ANOVA indicated a significant effect of Asenapine (F1,55= 0.17, P<.01) on the potency of LP‐44 (F5,55=61.90, P<.001), and a significant interaction effect (F5,55=5.38, P<.001).

Reference: CNS Neurosci Ther. 2017 Jun; 23(6): 518–525. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492759/

Formulation protocol:

1. Wu HH, Meng TT, Chen JM, Meng FL, Wang SY, Liu RH, Chen JN, Ning B, Li Y, Su GH. Asenapine maleate inhibits angiotensin II-induced proliferation and activation of cardiac fibroblasts via the ROS/TGFβ1/MAPK signaling pathway. Biochem Biophys Res Commun. 2021 May 14;553:172-179. doi: 10.1016/j.bbrc.2021.03.042. Epub 2021 Mar 24. PMID: 33773140. 2. Grossini E, Gramaglia C, Farruggio S, Camillo L, Mary D, Vacca G, Zeppegno P. Asenapine modulates nitric oxide release and calcium movements in cardiomyoblasts. J Pharmacol Pharmacother. 2016 Jan-Mar;7(1):6-14. doi: 10.4103/0976-500X.179358. PMID: 27127388; PMCID: PMC4831496. 3. Foute Nelong T, Manduca JD, Zonneveld PM, Perreault ML. Asenapine maleate normalizes low frequency oscillatory deficits in a neurodevelopmental model of schizophrenia. Neurosci Lett. 2019 Oct 15;711:134404. doi: 10.1016/j.neulet.2019.134404. Epub 2019 Jul 26. PMID: 31356843. 4. Delcourte S, Abrial E, Etiévant A, Rovera R, Arnt J, Didriksen M, Haddjeri N. Asenapine modulates mood-related behaviors and 5-HT1A/7 receptors-mediated neurotransmission. CNS Neurosci Ther. 2017 Jun;23(6):518-525. doi: 10.1111/cns.12698. Epub 2017 Apr 17. PMID: 28417559; PMCID: PMC6492759.

In vitro protocol:

1. Wu HH, Meng TT, Chen JM, Meng FL, Wang SY, Liu RH, Chen JN, Ning B, Li Y, Su GH. Asenapine maleate inhibits angiotensin II-induced proliferation and activation of cardiac fibroblasts via the ROS/TGFβ1/MAPK signaling pathway. Biochem Biophys Res Commun. 2021 May 14;553:172-179. doi: 10.1016/j.bbrc.2021.03.042. Epub 2021 Mar 24. PMID: 33773140. 2. Grossini E, Gramaglia C, Farruggio S, Camillo L, Mary D, Vacca G, Zeppegno P. Asenapine modulates nitric oxide release and calcium movements in cardiomyoblasts. J Pharmacol Pharmacother. 2016 Jan-Mar;7(1):6-14. doi: 10.4103/0976-500X.179358. PMID: 27127388; PMCID: PMC4831496.

In vivo protocol:

1. Foute Nelong T, Manduca JD, Zonneveld PM, Perreault ML. Asenapine maleate normalizes low frequency oscillatory deficits in a neurodevelopmental model of schizophrenia. Neurosci Lett. 2019 Oct 15;711:134404. doi: 10.1016/j.neulet.2019.134404. Epub 2019 Jul 26. PMID: 31356843. 2. Delcourte S, Abrial E, Etiévant A, Rovera R, Arnt J, Didriksen M, Haddjeri N. Asenapine modulates mood-related behaviors and 5-HT1A/7 receptors-mediated neurotransmission. CNS Neurosci Ther. 2017 Jun;23(6):518-525. doi: 10.1111/cns.12698. Epub 2017 Apr 17. PMID: 28417559; PMCID: PMC6492759.

References:

1: Scheidemantel T, Korobkova I, Rej S, Sajatovic M. Asenapine for bipolar disorder. Neuropsychiatr Dis Treat. 2015 Dec 4;11:3007-17. doi: 10.2147/NDT.S78043. eCollection 2015. Review. PubMed PMID: 26674884; PubMed Central PMCID: PMC4675633.

2: Hay A, Byers A, Sereno M, Basra MK, Dutta S. Asenapine versus placebo for schizophrenia. Cochrane Database Syst Rev. 2015 Nov 24;(11):CD011458. doi: 10.1002/14651858.CD011458.pub2. Review. PubMed PMID: 26599405.

3: Dell'Osso B, Cremaschi L, Palazzo MC, Spagnolin G, Cattaneo A, Grancini B, Maggi M, Altamura AC. Use of asenapine as add-on therapy in the treatment of bipolar disorder: a comprehensive review and case series. Expert Opin Drug Saf. 2014 Sep;13(9):1199-208. doi: 10.1517/14740338.2014.938047. Epub 2014 Aug 1. Review. PubMed PMID: 25084462.

4: Citrome L. Asenapine review, part I: chemistry, receptor affinity profile, pharmacokinetics and metabolism. Expert Opin Drug Metab Toxicol. 2014 Jun;10(6):893-903. doi: 10.1517/17425255.2014.908185. Epub 2014 May 3. Review. PubMed PMID: 24793403.

5: Citrome L. Asenapine review, part II: clinical efficacy, safety and tolerability. Expert Opin Drug Saf. 2014 Jun;13(6):803-30. doi: 10.1517/14740338.2014.908183. Epub 2014 May 3. Review. PubMed PMID: 24793161.

6: Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU. Asenapine, blonanserin, iloperidone, lurasidone, and sertindole: distinctive clinical characteristics of 5 novel atypical antipsychotics. Clin Neuropharmacol. 2013 Nov-Dec;36(6):223-38. doi: 10.1097/WNF.0b013e3182aa38c4. Review. PubMed PMID: 24201235.

7: Cortese L, Bressan RA, Castle DJ, Mosolov SN. Management of schizophrenia: clinical experience with asenapine. J Psychopharmacol. 2013 Apr;27(4 Suppl):14-22. doi: 10.1177/1359786813482533. Epub 2013 Mar 27. Review. PubMed PMID: 23535351.

8: Young AH, Altamura AC, González-Pinto AM, Millet B, Wiedemann K. Use of asenapine in clinical practice for the management of bipolar mania. J Psychopharmacol. 2013 Apr;27(4 Suppl):3-13. doi: 10.1177/1359786813482534. Epub 2013 Mar 27. Review. PubMed PMID: 23535350.

9: Fagiolini A, Forgione RN, Morana B, Maccari M, Goracci A, Bossini L, Pellegrini F, Cuomo A, Casamassima F. Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice. Expert Opin Pharmacother. 2013 Mar;14(4):489-504. doi: 10.1517/14656566.2013.765859. Epub 2013 Jan 29. Review. PubMed PMID: 23356509.

10: Bobo WV. Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. Review. PubMed PMID: 23272794.

11: Asenapine: a less effective, yet, more dangerous neuroleptic! Prescrire Int. 2012 Oct;21(131):229-32. Review. PubMed PMID: 23185842.

12: Tarazi FI, Neill JC. The preclinical profile of asenapine: clinical relevance for the treatment of schizophrenia and bipolar mania. Expert Opin Drug Discov. 2013 Jan;8(1):93-103. doi: 10.1517/17460441.2013.738193. Epub 2012 Nov 4. Review. PubMed PMID: 23121334.

13: De Hert M, Yu W, Detraux J, Sweers K, van Winkel R, Correll CU. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs. 2012 Sep 1;26(9):733-59. doi: 10.2165/11634500-000000000-00000. Review. PubMed PMID: 22900950.

14: Tarazi FI, Stahl SM. Iloperidone, asenapine and lurasidone: a primer on their current status. Expert Opin Pharmacother. 2012 Sep;13(13):1911-22. doi: 10.1517/14656566.2012.712114. Epub 2012 Jul 31. Review. PubMed PMID: 22849428.

15: Samalin L, Tixeront C, Llorca PM. [Asenapine in bipolar disorder: efficacy, safety and place in clinical practice]. Encephale. 2012 Jun;38(3):257-65. doi: 10.1016/j.encep.2012.05.001. Epub 2012 Jun 5. Review. French. Erratum in: Encephale. 2012 Oct;38(5):448-9. PubMed PMID: 22726414.

16: Stoner SC, Pace HA. Asenapine: a clinical review of a second-generation antipsychotic. Clin Ther. 2012 May;34(5):1023-40. doi: 10.1016/j.clinthera.2012.03.002. Epub 2012 Apr 10. Review. PubMed PMID: 22494521.

17: Potkin SG. Asenapine: a clinical overview. J Clin Psychiatry. 2011;72 Suppl 1:14-8. doi: 10.4088/JCP.10075su1.03. Review. PubMed PMID: 22217438.

18: McIntyre RS, Wong R. Asenapine: a synthesis of efficacy data in bipolar mania and schizophrenia. Clin Schizophr Relat Psychoses. 2012 Jan;5(4):217-20. doi: 10.3371/CSRP.5.4.6. Review. PubMed PMID: 22182459.

19: Pompili M, Serafini G, Innamorati M, Ambrosi E, Telesforo L, Venturini P, Giordano G, Battuello M, Lester D, Girardi P. Unmet treatment needs in schizophrenia patients: is asenapine a potential therapeutic option? Expert Rev Neurother. 2011 Jul;11(7):989-1006. doi: 10.1586/ern.11.82. Review. PubMed PMID: 21721916.

20: Citrome L. Iloperidone, asenapine, and lurasidone: a brief overview of 3 new second-generation antipsychotics. Postgrad Med. 2011 Mar;123(2):153-62. doi: 10.3810/pgm.2011.03.2273. Review. PubMed PMID: 21474903.

견적 문의: aibiohub@aibiohub.co.kr  홈페이지: www.aibiohub.co.kr 

견적 문의: https://aibiohub.co.kr/estimate/write