Itameline Explained
| Class: | Non-selective muscarinic acetylcholine receptor agonist |
| Cas Number: | 145071-44-9 |
| Cas Supplemental: |
145071-44-9 |
| Pubchem: | 9571042 |
| Chemspiderid: | 7845508 |
| Unii: | 5VO597V509 |
| Chembl: | 2105092 |
| Synonyms: | RU-47213; RU47213 |
| Iupac Name: | (4-chlorophenyl) 5-[(''E'')-methoxyiminomethyl]-3,6-dihydro-2H-pyridine-1-carboxylate |
| C: | 14 |
| H: | 15 |
| Cl: | 1 |
| N: | 2 |
| O: | 3 |
| Smiles: | CO/N=C/C1=CCCN(C1)C(=O)OC2=CC=C(C=C2)Cl |
| Stdinchi: | 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+ |
| Stdinchikey: | CTVQNEVLCGSTKL-CXUHLZMHSA-N |
Itameline (; 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]
The drug is a prodrug of RU-35963, an arecoline derivative.[6] It is an agonist of the muscarinic acetylcholine M1 receptor as well as of other muscarinic acetylcholine receptors.[7] [8] Itameline is described as being superior to arecoline in terms of potency, central selectivity, and duration of action. The drug shows antiamnesic effects in animals, for instance reversing scopolamine-induced memory deficits.[9] Structurally, it is a tetrahydropyridine similarly to xanomeline and milameline.[10]
Itameline was first described in the scientific literature by 1992. It was under development by Hoechst Marion Roussel and reached phase 2 clinical trials by 1998 prior to the discontinuation of its development.[11] [12]
Notes and References
- Web site: Delving into the Latest Updates on Itameline with Synapse . Synapse . 28 September 2024 . 26 October 2024.
- M'Harzi M, Willig F, Gieules C, Palou AM, Oberlander C, Barzaghi F . 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 . April 1997 . 9130292 . 10.1016/s0091-3057(96)00423-6 .
- Toja E, Bonetti C, Butti A, Hunt P, Fortin M, Barzaghi F, Formento ML, Maggioni A, Nencioni A, Galliani G . 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 . Elsevier BV . 27 . 5 . 1992 . 0223-5234 . 10.1016/0223-5234(92)90186-5 . 519–526.
- Froestl W, Muhs A, Pfeifer A . Cognitive enhancers (nootropics). Part 1: drugs interacting with receptors . Journal of Alzheimer's Disease . 32 . 4 . 793–887 . 2012 . 22886028 . 10.3233/JAD-2012-121186 .
- Fischer F, Matthisson M, Herrling P . List of drugs in development for neurodegenerative diseases . Neuro-Degenerative Diseases . 1 . 1 . 50–70 . 2004 . 16908974 . 10.1159/000077879 .
- Camps P, Muñoz-Torrero D . Cholinergic drugs in pharmacotherapy of Alzheimer's disease . Mini Reviews in Medicinal Chemistry . 2 . 1 . 11–25 . February 2002 . 12369954 . 10.2174/1389557023406638 .
- Palma JA . Muscarinic control of cardiovascular function in humans: a review of current clinical evidence . Clinical Autonomic Research . 34 . 1 . 31–44 . February 2024 . 38305989 . 10994193 . 10.1007/s10286-024-01016-5 .
- Korczyn AD . Muscarinic M(1) agonists in the treatment of Alzheimer's disease . Expert Opinion on Investigational Drugs . 9 . 10 . 2259–2267 . October 2000 . 11060805 . 10.1517/13543784.9.10.2259 .
- Deiana S, Platt B, Riedel G . The cholinergic system and spatial learning . Behavioural Brain Research . 221 . 2 . 389–411 . August 2011 . 21108971 . 10.1016/j.bbr.2010.11.036 .
- Mirza NR, Peters D, Sparks RG . Xanomeline and the antipsychotic potential of muscarinic receptor subtype selective agonists . CNS Drug Reviews . 9 . 2 . 159–186 . 2003 . 12847557 . 6741650 . 10.1111/j.1527-3458.2003.tb00247.x .
- Eglen RM, Hegde SS . Selective modulation of muscarinic receptor subtypes: therapeutic potential . Emerging Drugs . Informa Healthcare . 3 . 1 . 1998 . 1361-9195 . 10.1517/14728214.3.1.67 . 67–80.
- Saklani A, Kutty SK . Plant-derived compounds in clinical trials . Drug Discovery Today . 13 . 3–4 . 161–171 . February 2008 . 18275914 . 10.1016/j.drudis.2007.10.010 .
