Muscarinic agonist
Pharmaceutical compound
Itameline (INN Tooltip International Nonproprietary Name ; developmental code nameRU-47213 ) is anon-selective muscarinic acetylcholine receptor agonist which was under development for the treatment ofAlzheimer's disease andmemory disorders but was never marketed.[ 1] [ 2] [ 3] nootropic " (cognitive enhancer).[ 4] [ 5]
The drug is aprodrug ofRU-35963 , anarecoline derivative .[ 6] [ 7] [ 2] M1 receptor as well as of other muscarinic acetylcholine receptors.[ 8] [ 6] [ 9] [ 7] [ 2] potency ,central selectivity , andduration of action .[ 6] [ 7] antiamnesic effects in animals, for instance reversingscopolamine -inducedmemory deficits .[ 10] [ 6] [ 2] [ 3] Structurally , it is atetrahydropyridine similarly toxanomeline andmilameline .[ 11]
Itameline was first described in thescientific literature by 1992.[ 3] Hoechst Marion Roussel and reachedphase 2 clinical trials by 1998 prior to the discontinuation of its development.[ 12] [ 7] [ 4]
^ "Delving into the Latest Updates on Itameline with Synapse" .Synapse . 28 September 2024. Retrieved26 October 2024 .^a b c d 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 . ^a b c 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 . ^a b 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 . ^ 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 . ^a b c d 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 . ^a b c d 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 .
mAChRs Tooltip Muscarinic acetylcholine receptors
Agonists Antagonists 3-Quinuclidinyl benzilate 4-DAMP Aclidinium bromide (+formoterol )Abediterol AF-DX 250 AF-DX 384 Ambutonium bromide Anisodamine Anisodine Antihistamines (first-generation) (e.g.,brompheniramine ,buclizine ,captodiame ,chlorphenamine (chlorpheniramine) ,cinnarizine ,clemastine ,cyproheptadine ,dimenhydrinate ,dimetindene ,diphenhydramine ,doxylamine ,meclizine ,mequitazine ,perlapine ,phenindamine ,pheniramine ,phenyltoloxamine ,promethazine ,propiomazine ,triprolidine )AQ-RA 741 Atropine Atropine methonitrate Atypical antipsychotics (e.g.,clozapine ,fluperlapine ,olanzapine (+fluoxetine ),rilapine ,quetiapine ,tenilapine ,zotepine )Benactyzine Benzatropine (benztropine) Benzilone Benzilylcholine mustard Benzydamine Bevonium BIBN 99 Biperiden Bornaprine Camylofin CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,368 CAR-302,537 CAR-302,668 Caramiphen Cimetropium bromide Clidinium bromide Cloperastine CS-27349 Cyclobenzaprine Cyclopentolate Darifenacin DAU-5884 Desfesoterodine Dexetimide DIBD Dicycloverine (dicyclomine) Dihexyverine Difemerine Diphemanil metilsulfate Ditran Drofenine EA-3167 EA-3443 EA-3580 EA-3834 Emepronium bromide Etanautine Etybenzatropine (ethybenztropine) Fenpiverinium Fentonium bromide Fesoterodine Flavoxate Glycopyrronium bromide (+beclometasone/formoterol ,+indacaterol ,+neostigmine )Hexahydrodifenidol Hexahydrosiladifenidol Hexbutinol Hexocyclium Himbacine HL-031,120 Homatropine Imidafenacin Ipratropium bromide (+salbutamol )Isopropamide J-104,129 Hyoscyamine Mamba toxin 3 Mamba toxin 7 Mazaticol Mebeverine Meladrazine Mepenzolate Methantheline Methoctramine Methylatropine Methylhomatropine Methylscopolamine Metixene Muscarinic toxin 7 N-Ethyl-3-piperidyl benzilate N-Methyl-3-piperidyl benzilate Nefopam Octatropine methylbromide (anisotropine methylbromide) Orphenadrine Otenzepad (AF-DX 116) Otilonium bromide Oxapium iodide Oxitropium bromide Oxybutynin Oxyphencyclimine Oxyphenonium bromide PBID PD-102,807 PD-0298029 Penthienate Pethidine pFHHSiD Phenglutarimide Phenyltoloxamine Pipenzolate bromide Piperidolate Pirenzepine Piroheptine Pizotifen Poldine Pridinol Prifinium bromide Procyclidine Profenamine (ethopropazine) Propantheline bromide Propiverine Quinidine 3-Quinuclidinyl thiochromane-4-carboxylate Revefenacin Rociverine RU-47,213 SCH-57,790 SCH-72,788 SCH-217,443 Scopolamine (hyoscine) Scopolamine butylbromide (hyoscine butylbromide) Silahexacyclium Sofpironium bromide Solifenacin SSRIs Tooltip Selective serotonin reuptake inhibitors (e.g.,femoxetine ,paroxetine )Telenzepine Terodiline Tetracyclic antidepressants (e.g.,amoxapine ,maprotiline ,mianserin ,mirtazapine )Tiemonium iodide Timepidium bromide Tiotropium bromide Tiquizium bromide Tofenacin Tolterodine Tricyclic antidepressants (e.g.,amitriptyline (+perphenazine ),amitriptylinoxide ,butriptyline ,cidoxepin ,clomipramine ,desipramine ,desmethyldesipramine ,dibenzepin ,dosulepin (dothiepin) ,doxepin ,imipramine ,lofepramine ,nitroxazepine ,northiaden (desmethyldosulepin) ,nortriptyline ,protriptyline ,quinupramine ,trimipramine )Tridihexethyl Trihexyphenidyl Trimebutine Tripitamine (tripitramine) Tropacine Tropatepine Tropicamide Trospium chloride Typical antipsychotics (e.g.,chlorpromazine ,chlorprothixene ,cyamemazine (cyamepromazine) ,loxapine ,mesoridazine ,thioridazine )Umeclidinium bromide (+vilanterol )WIN-2299 Xanomeline Zamifenacin
Precursors (andprodrugs )
