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Nemonapride

Nemonapride
Clinical data
Trade namesEmilace (JP, CN)
Other namesEmonapride; Emirace; YM 09151-2; YM09151-2; YM 09151; YM09151
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral[1][2]
Drug classDopamine D2, D3, and D4 receptor antagonist; Serotonin 5-HT1A receptor partial agonist; Antipsychotic
ATC code
  • None
Legal status
Legal status
  • Rx-only (JP)
Pharmacokinetic data
MetabolismPrimarily CYP3A4[2]
Elimination half-life2.3–4.5 hours[2]
Identifiers
  • N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H26ClN3O2
Molar mass387.91 g·mol−1
3D model (JSmol)
  • CC1C(CCN1CC2=CC=CC=C2)NC(=O)C3=CC(=C(C=C3OC)NC)Cl
  • InChI=1S/C21H26ClN3O2/c1-14-18(9-10-25(14)13-15-7-5-4-6-8-15)24-21(26)16-11-17(22)19(23-2)12-20(16)27-3/h4-8,11-12,14,18,23H,9-10,13H2,1-3H3,(H,24,26)
  • Key:KRVOJOCLBAAKSJ-UHFFFAOYSA-N
  (verify)

Nemonapride, also previously known as emonapride and sold under the brand name Emilace, is an atypical antipsychotic which is used in the treatment of schizophrenia.[1][2][3] It is taken by mouth.[1][2]

Side effects of nemonapride include akathisia, dystonia, hypokinesia, tremor, hypersalivation, and hyperprolactinemia, among others.[1][2] The drug acts as a dopamine D2, D3, and D4 receptor antagonist.[1] To a lesser extent, it is also a serotonin 5-HT1A receptor partial agonist.[4] Structurally, nemonapride is a benzamide derivative and is related to sulpiride and other benzamides.[1]

Nemonapride was introduced for medical use in either 1991[5] or 1997.[1][6] It was developed and marketed by Yamanouchi Pharmaceuticals.[6][7] The drug is approved only in Japan and China.[8]

Medical uses

Nemonapride is used in the treatment of schizophrenia.[1][2] It is described as being effective in treating the positive symptoms of schizophrenia.[1] It is also said to have some antidepressant and anxiolytic effects.[1] However, clinical data on nemonapride are described as being somewhat limited.[1]

Available forms

Nemonapride is available in the form of 3 and 10 mg oral tablets.[2]

Side effects

Side effects of nemonapride include akathisia, dystonia, hypokinesia, tremor, hypersalivation, and hyperprolactinemia, among others.[1][2]

Pharmacology

Pharmacodynamics

Nemonapride has been described both as a typical antipsychotic[1] and as an atypical antipsychotic.[9] It is a potent and selective dopamine D2, D3, and D4 receptor antagonist.[1] Its affinities (Ki) for these receptors are 0.16 nM for the dopamine D2 receptor, 0.26 nM for the dopamine D3 receptor, and 0.31 nM for the dopamine D4 receptor.[1] Antagonism of the dopamine D2 receptor is thought to be responsible for the antipsychotic effects of nemonapride.[2]

In addition to the dopamine D2-like receptors, nemonapride has weaker affinity for the serotonin 5-HT1A and 5-HT2A receptors.[1] Its affinities (Ki) for these receptors are 1.8 nM for the serotonin 5-HT1A receptor (11-fold lower than for the D2 receptor) and 9.4 nM for the serotonin 5-HT2A receptor (59-fold lower than for the D2 receptor).[1] It is a partial agonist of the serotonin 5-HT1A receptor.[10][1][11] It has very weak affinity for sigma receptors (Ki = 80–3,000 nM) as well.[12] Besides these specific receptors, nemonapride is described as having very weak affinity for the dopamine D1, serotonin 5-HT2, adrenergic, and cholinergic receptors.[1]

In animals, nemonapride suppresses conditioned avoidance responses, inhibits methamphetamine- and apomorphine-induced hyperactivity and stereotypy, produces catalepsy, and has slight central depressant effects.[1][2]

Pharmacokinetics

Nemonapride is metabolized primarily by the cytochrome P450 enzyme CYP3A4.[2] Its elimination half-life is 2.3 to 4.5 hours.[2]

Chemistry

Nemonapride is a benzamide derivative and is structurally related to other dopamine antagonists of the benzamide group such as sulpiride.[1]

Structure and stereochemistry

Nemonapride is a cis-2-methyl-3-amino-pyrrolidine derivative,[13] which was later shown to express most of its action as a drug to treat schizophrenia from its homochiral (+)-(2R,3R) form.[14][15]

History

Nemonapride was developed by scientists at Yamanouchi Pharmaceuticals via structural modification of the benzamide antiemetic and gastroprokinetic agent metoclopramide.[6][13] It was first described in the scientific literature by 1980.[16] The name nemonapride was first used by 1989 and this name was designated as its INNTooltip International Nonproprietary Name in 1991.[17][18] The drug was launched in May 1991.[5] However, other sources state that it was launched in 1997.[1][6]

Society and culture

Names

Nemonapride is the generic name of the drug and its INNTooltip International Nonproprietary Name and JANTooltip Japanese Accepted Name.[8][7][19] It was also previously known as emonapride and by its former developmental code name YM 09151-2.[8][7][19][20] In addition, nemonapride is known by its brand name Emilace (JPTooltip Japanese language: エミレース) in Japan and China.[8][7][19]

Availability

Nemonapride is marketed only in Japan and China.[8][7] It was also under development for use in other countries, such as France, but development in other countries was discontinued.[3][1] There are no further plans for nemonapride to be developed for use in the United States, the United Kingdom, or Europe.[1]

See also

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x Bishara D, Taylor D (2008). "Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability". Drugs. 68 (16): 2269–2292. doi:10.2165/0003495-200868160-00002. PMID 18973393.
  2. ^ a b c d e f g h i j k l m "医療用医薬品 : エミレース (エミレース錠3mg 他)". KEGG (in Japanese). 18 September 2024. Retrieved 24 October 2024.
  3. ^ a b "Nemonapride". AdisInsight. 6 June 2007. Retrieved 24 October 2024.
  4. ^ Kusumi I, Boku S, Takahashi Y (May 2015). "Psychopharmacology of atypical antipsychotic drugs: From the receptor binding profile to neuroprotection and neurogenesis". Psychiatry and Clinical Neurosciences. 69 (5). Wiley: 243–258. doi:10.1111/pcn.12242. PMID 25296946. S2CID 23102204.
  5. ^ a b "Pharmaceuticals and Medical Devices Safety Information No. 265" (PDF). Pharmaceuticals and Medical Devices Agency. January 2010. Archived from the original (PDF) on 26 July 2022. Retrieved 26 July 2022.
  6. ^ a b c d Burke A, Marques C, Turner N, Hermann G (2018). Active Pharmaceutical Ingredients in Synthesis: Catalytic Processes in Research and Development. Wiley. p. 380. ISBN 978-3-527-34241-9. Retrieved 24 October 2024.
  7. ^ a b c d e Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 845. ISBN 978-3-88763-101-7. Retrieved 24 October 2024.
  8. ^ a b c d e "Nemonapride". Drugs.com. Archived from the original on 2016-03-03.
  9. ^ MacDonald GJ, Bartolomé JM (2010). "A decade of progress in the discovery and development of 'atypical' antipsychotics". Prog Med Chem. Progress in Medicinal Chemistry. 49: 37–80. doi:10.1016/S0079-6468(10)49002-5. ISBN 978-0-12-381292-6. PMID 20855038.
  10. ^ Newman-Tancredi A, Kleven MS (August 2011). "Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties". Psychopharmacology (Berl). 216 (4): 451–473. doi:10.1007/s00213-011-2247-y. PMID 21394633.
  11. ^ Assié MB, Cosi C, Koek W (September 1997). "5-HT1A receptor agonist properties of the antipsychotic, nemonapride: comparison with bromerguride and clozapine". Eur J Pharmacol. 334 (2–3): 141–147. doi:10.1016/s0014-2999(97)01207-7. PMID 9369342.
  12. ^ Wilson JM, Sanyal S, Van Tol HH (June 1998). "Dopamine D2 and D4 receptor ligands: relation to antipsychotic action". Eur J Pharmacol. 351 (3): 273–286. doi:10.1016/s0014-2999(98)00312-4. PMID 9721018.
  13. ^ a b Iwanami S, Takashima M, Hirata Y, Hasegawa O, Usuda S (October 1981). "Synthesis and neuroleptic activity of benzamides. Cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds". Journal of Medicinal Chemistry. 24 (10). American Chemical Society (ACS): 1224–1230. doi:10.1021/jm00142a019. PMID 6120234.
  14. ^ Harada S, Sakai T, Takasu K, Yamada K, Yamamoto Y, Tomioka K (September 2012). "General entry to asymmetric one-pot [N + 2 + n] cyclization for the synthesis of three- to seven-membered azacycloalkanes". The Journal of Organic Chemistry. 77 (17). American Chemical Society (ACS): 7212–7222. doi:10.1021/jo301495a. PMID 22894619.
  15. ^ Uesugi SI, Sasano Y, Matsui S, Kanoh N, Iwabuchi Y (2017). "Concise, Protecting-Group-Free Synthesis of (+)-Nemonapride via Eu(OTf)3-Catalyzed Aminolysis of 3,4-Epoxy Alcohol". Chemical & Pharmaceutical Bulletin. 65 (1). Pharmaceutical Society of Japan: 22–24. doi:10.1248/cpb.c16-00568. PMID 28049911.
  16. ^ Usuda S, Maeno H (January 1980). "Pharmacological Properties of a New Benzamide, YM-09151-2 With Potentially Neuroleptic Actions". Infolia Pharmacologica Japonica. 76 (7). Japan: Japanese Pharmacological Soc.: 184–185.
  17. ^ Mori A, Kazamatsuri H, Kaneno S, Kamijima K, Kariya T, Murasaki M, et al. (1989). "A double-blind comparison of a new benzamide compound YM-09151 with haloperidol in the treatment of schizophrenia". Clin Eval. 17: 349–377.
  18. ^ "International Nonproprietary Names for Pharmaceutical Substances" (PDF). WHO Drug Information. 5 (3). 1991.
  19. ^ a b c Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 191. ISBN 978-94-011-4439-1. Retrieved 24 October 2024.
  20. ^ "-pride: sulpiride derivatives and analogues" (PDF). Use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. World Health Organization (WHO). 2024.
Index: pl ar de en es fr it arz nl ja pt ceb sv uk vi war zh ru af ast az bg zh-min-nan bn be ca cs cy da et el eo eu fa gl ko hi hr id he ka la lv lt hu mk ms min no nn ce uz kk ro simple sk sl sr sh fi ta tt th tg azb tr ur zh-yue hy my ace als am an hyw ban bjn map-bms ba be-tarask bcl bpy bar bs br cv nv eml hif fo fy ga gd gu hak ha hsb io ig ilo ia ie os is jv kn ht ku ckb ky mrj lb lij li lmo mai mg ml zh-classical mr xmf mzn cdo mn nap new ne frr oc mhr or as pa pnb ps pms nds crh qu sa sah sco sq scn si sd szl su sw tl shn te bug vec vo wa wuu yi yo diq bat-smg zu lad kbd ang smn ab roa-rup frp arc gn av ay bh bi bo bxr cbk-zam co za dag ary se pdc dv dsb myv ext fur gv gag inh ki glk gan guw xal haw rw kbp pam csb kw km kv koi kg gom ks gcr lo lbe ltg lez nia ln jbo lg mt mi tw mwl mdf mnw nqo fj nah na nds-nl nrm nov om pi pag pap pfl pcd krc kaa ksh rm rue sm sat sc trv stq nso sn cu so srn kab roa-tara tet tpi to chr tum tk tyv udm ug vep fiu-vro vls wo xh zea ty ak bm ch ny ee ff got iu ik kl mad cr pih ami pwn pnt dz rmy rn sg st tn ss ti din chy ts kcg ve
Prefix: a b c d e f g h i j k l m n o p q r s t u v w x y z 0 1 2 3 4 5 6 7 8 9

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