Design, synthesis, and biological activity of methoctramine-related tetraamines bearing an 11-acetyl-5,11-dihydro-6H-pyrido[2,3-b][1,4] benzodiazepin-6-one moiety: structural requirements for optimum occupancy of muscarinic receptor subtypes as revealed by symmetrical and unsymmetrical polyamines.

@article{Minarini1994DesignSA,
  title={Design, synthesis, and biological activity of methoctramine-related tetraamines bearing an 11-acetyl-5,11-dihydro-6H-pyrido[2,3-b][1,4] benzodiazepin-6-one moiety: structural requirements for optimum occupancy of muscarinic receptor subtypes as revealed by symmetrical and unsymmetrical polyamines.},
  author={Anna Minarini and Mar{\'i}a Laura Bolognesi and Roberta Budriesi and Marco Canossa and Alberto Chiarini and Santi Spampinato and Carlo Melchiorre},
  journal={Journal of medicinal chemistry},
  year={1994},
  volume={37 20},
  pages={
          3363-72
        }
}
Tetraamines 5-13 and diamines 14-17 as well as monoamine 18 were synthesized, and their biological profiles at muscarinic receptor subtypes were assessed by functional experiments in isolated guinea pig left atrium (M2) and ileum (M3) and by binding assays in rat cortex (M1), heart (M2), and submaxillary gland (M3) homogenates and NG 108-15 cells (M4). An appropriate number and type of substituents on the terminal nitrogens of a tetraamine backbone afforded compounds, such as tripitramine (8… 
Polymethylene tetraamine backbone as template for the development of biologically active polyamines
TLDR
The universal template approach formed the basis for modifying benextramine structure to the design of ligands, which display affinity for acetylcholinesterase and muscarinic M2 receptors and could have potential in the investigation of Alzheimer disease.
Synthetic polyamines: an overview of their multiple biological activities
TLDR
Several application of this design strategy aimed at discovering potent and selective polyamines able to bind neurotransmitter receptors and enzymes, such as muscarinic receptor subtypes, muscle-type nicotinic receptors and acethylcholinesterase are detailed.
Evidence for muscarinic M4 receptors mediating nonadrenergic noncholinergic relaxations in rabbit anococcygeus muscle
TLDR
Relaxations induced by the stimulation of muscarinic and nicotinic AchRs as well as by electrical field stimulation were completely abolished by tetrodotoxin and were also sensitive to the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NOARG), indicating that NO plays an important role as an inhibitory NANC transmitter in RAM.
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