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Selective M2 receptor antagonist
Pharmaceutical compound
Tripitramine Other names Tripitamine Drug class Muscarinic acetylcholine receptor antagonist ; Selective muscarinic acetylcholine M2 receptor antagonist
11-[2-[6-[8-[6-[bis[2-oxo-2-(6-oxo-5H -pyrido[2,3-b][1,4]benzodiazepin-11-yl)ethyl]amino]hexyl-methylamino]octyl-methylamino]hexylamino]acetyl]-5H -pyrido[2,3-b][1,4]benzodiazepin-6-one
CAS Number PubChem CID IUPHAR/BPS ChemSpider ChEMBL CompTox Dashboard (EPA ) Formula C 64 H 77 N 13 O 6 Molar mass 124 .405−1 3D model (JSmol )
CN(CCCCCCCCN(C)CCCCCCN(CC(=O)N1C2=CC=CC=C2C(=O)NC3=C1N=CC=C3)CC(=O)N4C5=CC=CC=C5C(=O)NC6=C4N=CC=C6)CCCCCCNCC(=O)N7C8=CC=CC=C8C(=O)NC9=C7N=CC=C9
InChI=1S/C64H77N13O6/c1-72(41-20-8-5-17-35-65-44-56(78)75-53-32-14-11-26-47(53)62(81)69-50-29-23-36-66-59(50)75)39-18-6-3-4-7-19-40-73(2)42-21-9-10-22-43-74(45-57(79)76-54-33-15-12-27-48(54)63(82)70-51-30-24-37-67-60(51)76)46-58(80)77-55-34-16-13-28-49(55)64(83)71-52-31-25-38-68-61(52)77/h11-16,23-34,36-38,65H,3-10,17-22,35,39-46H2,1-2H3,(H,69,81)(H,70,82)(H,71,83)
Key:YUJOQEAGGUIMED-UHFFFAOYSA-N
Tripitramine , or tripitamine , is an antimuscarinic drug which was never marketed.[ 1] [ 2] [ 3] [ 4]
The drug is a selective antagonist of the muscarinic acetylcholine M2 receptor .[ 1] [ 2] [ 3] [ 5] [ 6] affinities (Ki ) for the muscarinic acetylcholine receptors are 0.27 nM for the M2 receptor, 1.58 nM for the M1 receptor (5.9-fold less than for M2 ), 6.41 nM for the M4 receptor (24-fold less than for M2 ), 33.87 nM for the M5 receptor (125-fold less than for M2 ), and 38.25 nM for the M3 receptor (142-fold less than for M2 ).[ 2] [ 5] cardioselective and to increase heart rate in animals.[ 1] [ 7]
Structurally , it consists of three pirenzepine - or AQ-RA 741 -like tricyclic (more specifically pyridobenzodiazepine) moieties bound together by a long amine -containing hydrocarbon chain similar to the one found within methoctramine (a modestly M2 -selective antimuscarinic agent).[ 1] [ 8] [ 4] dipitramine , spirotramine , caproctamine , and benextramine , among others.[ 1]
Tripitramine was first described in the scientific literature by 1993.[ 4] 2 receptor antagonists than methoctramine.[ 1] [ 4]
^ a b c d e f Melchiorre C, Antonello A, Banzi R, Bolognesi ML, Minarini A, Rosini M, et al. (March 2003). "Polymethylene tetraamine backbone as template for the development of biologically active polyamines". Medicinal Research Reviews . 23 (2): 200–233. doi :10.1002/med.10029 . PMID 12500289 . ^ a b c Zlotos DP, Bender W, Holzgrabe U (1999). "Muscarinic receptor agonists and antagonists". Expert Opinion on Therapeutic Patents . 9 (8). Informa Healthcare: 1029–1053. doi :10.1517/13543776.9.8.1029 . ISSN 1354-3776 . ^ a b Eglen RM, Watson N (February 1996). "Selective muscarinic receptor agonists and antagonists". Pharmacology & Toxicology . 78 (2): 59–68. doi :10.1111/j.1600-0773.1996.tb00181.x . PMID 8822036 . ^ a b c d Melchiorre C, Bolognesi ML, Chiarini A, Minarini A, Spampinato S (November 1993). "Synthesis and biological activity of some methoctramine-related tetraamines bearing a 11-acetyl-5,11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepin-6-one moiety as antimuscarinics: a second generation of highly selective M2 muscarinic receptor antagonists". Journal of Medicinal Chemistry . 36 (23): 3734–3737. doi :10.1021/jm00075a032 . PMID 8246244 . ^ a b Maggio R, Barbier P, Bolognesi ML, Minarini A, Tedeschi D, Melchiorre C (August 1994). "Binding profile of the selective muscarinic receptor antagonist tripitramine". European Journal of Pharmacology . 268 (3): 459–462. doi :10.1016/0922-4106(94)90075-2 . PMID 7805774 . ^ Chiarini A, Budriesi R, Bolognesi ML, Minarini A, Melchiorre C (April 1995). "In vitro characterization of tripitramine, a polymethylene tetraamine displaying high selectivity and affinity for muscarinic M2 receptors" . British Journal of Pharmacology . 114 (7): 1507–1517. doi :10.1111/j.1476-5381.1995.tb13378.x . PMC 1510296 PMID 7606355 . ^ Angeli P, Cantalamessa F, Gulini U, Melchiorre C (September 1995). "Selective blockade of muscarinic M2 receptors in vivo by the new antagonist tripitramine". Naunyn-Schmiedeberg's Archives of Pharmacology . 352 (3): 304–307. doi :10.1007/BF00168561 . PMID 8584046 . ^ "Tripitramine" . PubChem . Retrieved 27 October 2024 .
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 (and prodrugs )
