Chemistry:Tripitramine
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
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Polymethylene tetraamine backbone as template for the development of biologically active polyamines". Medicinal Research Reviews 23 (2): 200–233. March 2003. doi:10.1002/med.10029. PMID 12500289.
- ↑ 2.0 2.1 2.2 "Muscarinic receptor agonists and antagonists". Expert Opinion on Therapeutic Patents (Informa Healthcare) 9 (8): 1029–1053. 1999. doi:10.1517/13543776.9.8.1029. ISSN 1354-3776.
- ↑ 3.0 3.1 "Selective muscarinic receptor agonists and antagonists". Pharmacology & Toxicology 78 (2): 59–68. February 1996. doi:10.1111/j.1600-0773.1996.tb00181.x. PMID 8822036.
- ↑ 4.0 4.1 4.2 4.3 "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. November 1993. doi:10.1021/jm00075a032. PMID 8246244.
- ↑ 5.0 5.1 "Binding profile of the selective muscarinic receptor antagonist tripitramine". European Journal of Pharmacology 268 (3): 459–462. August 1994. doi:10.1016/0922-4106(94)90075-2. PMID 7805774.
- ↑ "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. April 1995. doi:10.1111/j.1476-5381.1995.tb13378.x. PMID 7606355.
- ↑ "Selective blockade of muscarinic M2 receptors in vivo by the new antagonist tripitramine". Naunyn-Schmiedeberg's Archives of Pharmacology 352 (3): 304–307. September 1995. doi:10.1007/BF00168561. PMID 8584046.
- ↑ "Tripitramine". https://pubchem.ncbi.nlm.nih.gov/compound/132947.
 |  |
