Tripitramine

Not to be confused with Trimipramine or Tryptamine.
Tripitramine
Clinical data
Other namesTripitamine
Drug classMuscarinic acetylcholine receptor antagonist; Selective muscarinic acetylcholine M2 receptor antagonist
Identifiers
  • 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)
Chemical and physical data
FormulaC64H77N13O6
Molar mass1124.405 g·mol−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]

Pharmacology

The drug is a selective antagonist of the muscarinic acetylcholine M2 receptor.[1][2][3][5][6] Its 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] Tripitramine has been found to be cardioselective and to increase heart rate in animals.[1][7]

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).[1][8][4] Related compounds with analogous structural designs include dipitramine, spirotramine, caproctamine, and benextramine, among others.[1]

History

Tripitramine was first described in the scientific literature by 1993.[4] It was developed in efforts to discover more highly selective M2 receptor antagonists than methoctramine.[1][4]

References

  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ "Tripitramine". PubChem. Retrieved 27 October 2024.