Itameline

Last updated

Itameline
Itameline.svg
Clinical data
Other namesRU-47213; RU47213
Drug class Non-selective muscarinic acetylcholine receptor agonist
Identifiers
  • (4-chlorophenyl) 5-[(E)-methoxyiminomethyl]-3,6-dihydro-2H-pyridine-1-carboxylate
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C14H15ClN2O3
Molar mass 294.74 g·mol−1
3D model (JSmol)
  • CO/N=C/C1=CCCN(C1)C(=O)OC2=CC=C(C=C2)Cl
  • InChI=1S/C14H15ClN2O3/c1-19-16-9-11-3-2-8-17(10-11)14(18)20-13-6-4-12(15)5-7-13/h3-7,9H,2,8,10H2,1H3/b16-9+
  • Key:CTVQNEVLCGSTKL-CXUHLZMHSA-N

Itameline (INN Tooltip International Nonproprietary Name; developmental code name RU-47213) is a non-selective muscarinic acetylcholine receptor agonist which was under development for the treatment of Alzheimer's disease and memory disorders but was never marketed. [1] [2] [3] It has been referred to as a "nootropic" (cognitive enhancer). [4] [5]

Itameline is a prodrug of RU-35963, an arecoline derivative. [6] [7] [2] It is an agonist of the muscarinic acetylcholine M1 receptor as well as of other muscarinic acetylcholine receptors. [8] [6] [9] [7] [2] Itameline is described as being superior to arecoline in terms of potency, central selectivity, and duration of action. [6] [7] The drug shows antiamnesic effects in animals, for instance reversing scopolamine-induced memory deficits. [10] [6] [2] [3] Structurally, it is a tetrahydropyridine similarly to xanomeline and milameline. [11]

Itameline was first described in the scientific literature by 1992. [3] It was under development by Hoechst Marion Roussel and reached phase 2 clinical trials by 1998 prior to the discontinuation of its development. [12] [7] [4]

References

  1. ↑ "Delving into the Latest Updates on Itameline with Synapse". Synapse. 28 September 2024. Retrieved 26 October 2024.
  2. 1 2 3 4 M'Harzi M, Willig F, Gieules C, Palou AM, Oberlander C, Barzaghi F (April 1997). "Ameliorating effects of RU 47213, a novel oral and long-lasting cholinomimetic agent, on working memory impairments in rats". Pharmacology, Biochemistry, and Behavior. 56 (4): 663–668. doi:10.1016/s0091-3057(96)00423-6. PMID   9130292.
  3. 1 2 3 Toja E, Bonetti C, Butti A, Hunt P, Fortin M, Barzaghi F, et al. (1992). "1-substituted-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-alkyloximes as novel orally active and long-lasting muscarinic cholinergic agonists". European Journal of Medicinal Chemistry. 27 (5). Elsevier BV: 519–526. doi:10.1016/0223-5234(92)90186-5. ISSN   0223-5234.
  4. 1 2 Froestl W, Muhs A, Pfeifer A (2012). "Cognitive enhancers (nootropics). Part 1: drugs interacting with receptors". Journal of Alzheimer's Disease. 32 (4): 793–887. doi:10.3233/JAD-2012-121186. PMID   22886028.
  5. ↑ Fischer F, Matthisson M, Herrling P (2004). "List of drugs in development for neurodegenerative diseases". Neuro-Degenerative Diseases. 1 (1): 50–70. doi:10.1159/000077879. PMID   16908974.
  6. 1 2 3 4 Camps P, Muñoz-Torrero D (February 2002). "Cholinergic drugs in pharmacotherapy of Alzheimer's disease". Mini Reviews in Medicinal Chemistry. 2 (1): 11–25. doi:10.2174/1389557023406638. PMID   12369954.
  7. 1 2 3 4 Saklani A, Kutty SK (February 2008). "Plant-derived compounds in clinical trials". Drug Discovery Today. 13 (3–4): 161–171. doi:10.1016/j.drudis.2007.10.010. PMID   18275914.
  8. ↑ Palma JA (February 2024). "Muscarinic control of cardiovascular function in humans: a review of current clinical evidence". Clinical Autonomic Research. 34 (1): 31–44. doi:10.1007/s10286-024-01016-5. PMC   10994193 . PMID   38305989.
  9. ↑ Korczyn AD (October 2000). "Muscarinic M(1) agonists in the treatment of Alzheimer's disease". Expert Opinion on Investigational Drugs. 9 (10): 2259–2267. doi:10.1517/13543784.9.10.2259. PMID   11060805.
  10. ↑ Deiana S, Platt B, Riedel G (August 2011). "The cholinergic system and spatial learning". Behavioural Brain Research. 221 (2): 389–411. doi:10.1016/j.bbr.2010.11.036. PMID   21108971.
  11. ↑ Mirza NR, Peters D, Sparks RG (2003). "Xanomeline and the antipsychotic potential of muscarinic receptor subtype selective agonists". CNS Drug Reviews. 9 (2): 159–186. doi:10.1111/j.1527-3458.2003.tb00247.x. PMC   6741650 . PMID   12847557.
  12. ↑ Eglen RM, Hegde SS (1998). "Selective modulation of muscarinic receptor subtypes: therapeutic potential". Emerging Drugs. 3 (1). Informa Healthcare: 67–80. doi:10.1517/14728214.3.1.67. ISSN   1361-9195.
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