Tripitramine

{{Short description|Selective M2 receptor antagonist}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Distinguish|Trimipramine|Tryptamine}} {{Infobox drug | drug_name = | image = Tripitramine.svg | image_class = skin-invert-image | width = | caption =

<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = | class = Muscarinic acetylcholine receptor antagonist; Selective muscarinic acetylcholine M₂ receptor antagonist | ATC_prefix = | ATC_suffix =

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<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =

<!-- Identifiers --> | CAS_number = 152429-64-6 | CAS_supplemental = | PubChem = 132947 | PubChemSubstance = | IUPHAR_ligand = 361 | DrugBank = | ChemSpiderID = 117328 | UNII = | KEGG = | ChEBI = | ChEMBL = 265256 | NIAID_ChemDB = | PDB_ligand = | synonyms = Tripitamine

<!-- Chemical data --> | IUPAC_name = 11-[2-[6-[8-[6-[bis[2-oxo-2-(6-oxo-5''H''-pyrido[2,3-b][1,4]benzodiazepin-11-yl)ethyl]amino]hexyl-methylamino]octyl-methylamino]hexylamino]acetyl]-5''H''-pyrido[2,3-b][1,4]benzodiazepin-6-one | C=64 | H=77 | N=13 | O=6 | SMILES = 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 | StdInChI = 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) | StdInChIKey = YUJOQEAGGUIMED-UHFFFAOYSA-N }}

'''Tripitramine''', or '''tripitamine''', is an antimuscarinic drug which was never marketed.<ref name="MelchiorreAntonelloBanzi2003">{{cite journal | vauthors = Melchiorre C, Antonello A, Banzi R, Bolognesi ML, Minarini A, Rosini M, Tumiatti V | title = Polymethylene tetraamine backbone as template for the development of biologically active polyamines | journal = Medicinal Research Reviews | volume = 23 | issue = 2 | pages = 200–233 | date = March 2003 | pmid = 12500289 | doi = 10.1002/med.10029 }}</ref><ref name="ZlotosBenderHolzgrabe1999">{{cite journal | vauthors = Zlotos DP, Bender W, Holzgrabe U | title=Muscarinic receptor agonists and antagonists | journal=Expert Opinion on Therapeutic Patents | publisher=Informa Healthcare | volume=9 | issue=8 | year=1999 | issn=1354-3776 | doi=10.1517/13543776.9.8.1029 | pages=1029–1053}}</ref><ref name="EglenWatson1996">{{cite journal | vauthors = Eglen RM, Watson N | title = Selective muscarinic receptor agonists and antagonists | journal = Pharmacology & Toxicology | volume = 78 | issue = 2 | pages = 59–68 | date = February 1996 | pmid = 8822036 | doi = 10.1111/j.1600-0773.1996.tb00181.x }}</ref><ref name="MelchiorreBolognesiChiarini1993" />

== Pharmacology ==

The drug is a selective antagonist of the muscarinic acetylcholine M₂ receptor.<ref name="MelchiorreAntonelloBanzi2003" /><ref name="ZlotosBenderHolzgrabe1999" /><ref name="EglenWatson1996" /><ref name="MaggioBarbierBolognesi1994">{{cite journal | vauthors = Maggio R, Barbier P, Bolognesi ML, Minarini A, Tedeschi D, Melchiorre C | title = Binding profile of the selective muscarinic receptor antagonist tripitramine | journal = European Journal of Pharmacology | volume = 268 | issue = 3 | pages = 459–462 | date = August 1994 | pmid = 7805774 | doi = 10.1016/0922-4106(94)90075-2 }}</ref><ref name="ChiariniBudriesiBolognesi1995">{{cite journal | vauthors = Chiarini A, Budriesi R, Bolognesi ML, Minarini A, Melchiorre C | title = In vitro characterization of tripitramine, a polymethylene tetraamine displaying high selectivity and affinity for muscarinic M2 receptors | journal = British Journal of Pharmacology | volume = 114 | issue = 7 | pages = 1507–1517 | date = April 1995 | pmid = 7606355 | pmc = 1510296 | doi = 10.1111/j.1476-5381.1995.tb13378.x }}</ref> Its affinities (K_i) for the muscarinic acetylcholine receptors are 0.27{{nbsp}}nM for the M₂ receptor, 1.58{{nbsp}}nM for the M₁ receptor (5.9-fold less than for M₂), 6.41{{nbsp}}nM for the M₄ receptor (24-fold less than for M₂), 33.87{{nbsp}}nM for the M₅ receptor (125-fold less than for M₂), and 38.25{{nbsp}}nM for the M₃ receptor (142-fold less than for M₂).<ref name="ZlotosBenderHolzgrabe1999" /><ref name="MaggioBarbierBolognesi1994" /> Tripitramine has been found to be cardioselective and to increase heart rate in animals.<ref name="MelchiorreAntonelloBanzi2003" /><ref name="AngeliCantalamessaGulini1995">{{cite journal | vauthors = Angeli P, Cantalamessa F, Gulini U, Melchiorre C | title = Selective blockade of muscarinic M2 receptors in vivo by the new antagonist tripitramine | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 352 | issue = 3 | pages = 304–307 | date = September 1995 | pmid = 8584046 | doi = 10.1007/BF00168561 }}</ref>

== Chemistry ==

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).<ref name="MelchiorreAntonelloBanzi2003" /><ref name="PubChem">{{cite web | title=Tripitramine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/132947 | access-date=27 October 2024}}</ref><ref name="MelchiorreBolognesiChiarini1993" /> Related compounds with analogous structural designs include dipitramine, spirotramine, caproctamine, and benextramine, among others.<ref name="MelchiorreAntonelloBanzi2003" />

== History ==

Tripitramine was first described in the scientific literature by 1993.<ref name="MelchiorreBolognesiChiarini1993">{{cite journal | vauthors = Melchiorre C, Bolognesi ML, Chiarini A, Minarini A, Spampinato S | title = 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 = Journal of Medicinal Chemistry | volume = 36 | issue = 23 | pages = 3734–3737 | date = November 1993 | pmid = 8246244 | doi = 10.1021/jm00075a032 }}</ref> It was developed in efforts to discover more highly selective M₂ receptor antagonists than methoctramine.<ref name="MelchiorreAntonelloBanzi2003" /><ref name="MelchiorreBolognesiChiarini1993" />

== References == {{Reflist}}

{{Muscarinic acetylcholine receptor modulators}} {{Tricyclics}}

Category:Abandoned drugs Category:M1 receptor antagonists Category:M2 receptor antagonists Category:Pyridobenzodiazepines Category:Tricyclic compounds