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Chemical Compound Review

Lopac-D-104     (1,1-dimethyl-3,4,5,6- tetrahydro-2H...

Synonyms: Tocris-0482, AG-K-20073, SureCN2730650, CHEBI:73467, CHEBI:376139, ...
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Disease relevance of 81405-11-0

  • These results suggest that, after elimination of most of the M3 receptors with 4-DAMP mustard, the contractile response can be mediated by the pertussis toxin-sensitive M2 receptor [1].
  • NPC-14695 was more M3/M2 selective than diphenyl-acetoxy-4-methylpiperidine methiodide (4-DAMP) in vivo, which was determined from the reversal of bronchoconstriction and bradycardia after i.v. administration in anesthetized guinea pigs infused with methacholine, but was less potent than ipratropium or 4-DAMP [2].
  • 4-DAMP at 10 to 100 nM significantly reduced the electrically evoked tension responses by about the same degree in normal and obstructed bladders, without affecting the potassium contractures [3].
  • Methacholine hypotension and evoked sudomotor responses exhibited an M3 muscarinic receptor profile with the following potency relationships: atropine > or = 4-DAMP > pirenzepine >> gallamine [4].
  • Muscarinic receptors in N1E 115 mouse neuroblastoma cells were characterized by competition binding experiments using three agonists and five antagonists, including 4-DAMP and AF-DX 116, and by studying the effect of agonist stimulation on the cellular cAMP and cGMP content [5].

Psychiatry related information on 81405-11-0


High impact information on 81405-11-0


Chemical compound and disease context of 81405-11-0

  • Acetylcholine-induced desensitization was prevented by uncoupling of M(2) receptors from G(i) with pertussis toxin or by selective inactivation of M(3) receptors with N-2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP mustard) [14].
  • Pertussis toxin treatment had no significant inhibitory effect on the control contractile response to oxotremorine-M, but caused an 8.8-fold increase in the EC50 value measured after a 2-hr treatment with 4-DAMP mustard [1].
  • 3. The contractile response to mATP was pertussis toxin-insensitive, irreversibly antagonized by N-(2-chloroethyl)-4-piperidinyl diphenylacetate (4-DAMP mustard), and unaffected by the muscarinic M(2)/M(4) receptor selective antagonist AF-DX 116 (1 microM) [15].
  • Both pertussis toxin- and 4-DAMP mustard-treatment had little or no effect on histamine-induced contractions in control ileum [14].

Biological context of 81405-11-0


Anatomical context of 81405-11-0


Associations of 81405-11-0 with other chemical compounds

  • The M1, M1/M3, or M3 antagonists inhibited the EFS-evoked cholinergic contractile response in a concentration-dependent manner (4-DAMP > rispenzepine > pirenzepine), whereas methoctramine facilitated this response at low concentrations ( < 3 microM) [22].
  • Carbachol-induced MAPK activity was also completely inhibited by 4-DAMP in both species [25].
  • The M3 muscarinic receptor antagonist 4-DAMP effectively reversed muscarine-induced inhibition of IPSCs with an IC50 of 0.11 +/- 0.03 microM [26].
  • The indirect mechanism involves local ACh release, is potentiated by acetylcholinesterase inhibitors and blocked by atropine methylbromide and 4-DAMP mustard, an M(3) muscarinic receptor selective antagonist [27].
  • In bladders of spinal cord transected rats, 10 Hz stimulation-evoked release of ACh was also inhibited by atropine and 4-DAMP (5 nM) but not by pirenzepine (50 nM) [28].

Gene context of 81405-11-0

  • The effect was mimicked by the muscarinic M1 receptor antagonist pirenzepine, but not by the muscarinic M2 receptor antagonist methoctoramine or the muscarinic M3 receptor antagonist 4-DAMP (4-diphenyl-acetoxy-N-methylpiperidine methiodide) [29].
  • The enhancement of IL-2 production by Oxo-M was inhibited by 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) an ml/m3 receptor antagonist [30].
  • Treatment of wild-type and M2 knockout urinary bladder with N-2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP mustard) caused a large inhibition of the muscarinic contractile response [31].
  • M1 (pirenzepine), M2 (methoctramine) and M3 (4-DAMP and pf-HHSiD) muscarinic receptor antagonists significantly antagonized the response induced by a submaximal concentration of carbachol (100 microM.). The apparent pA2 values were atropine (9.4), 4-DAMP (9.2), pfHHSid (7.4), pirenzepine (6.9) and methoctramine (6.3) [32].
  • Only 4-DAMP inhibited carbachol-induced motilin release in perifused duodenal mucosal cells [33].

Analytical, diagnostic and therapeutic context of 81405-11-0

  • The muscarinic antagonist 4-DAMP, which inhibits vasodilatations evoked by submucosal cholinergic vasodilator neurons, blocked dilatations elicited by mucosal stimulation and balloon distension [34].
  • The cardiovascular response evoked by 1 nmol of CBH was blocked by local microinjection of the nonselective muscarinic receptor antagonist atropine (3 nmol) or the selective M(2)-muscarinic receptor antagonist 4-DAMP (2 nmol) [35].
  • The ability of selective (pirenzepine, UH-AH 371, AF-DX 116, methoctramine, AQ-RA 741, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and hexahydro-sila-difenidol (HHSiD)) and non-selective (atropine) antagonists to inhibit the constriction elicited by ACh was estimated [36].
  • Baseline measurements (of outflow facility by two-level constant pressure perfusion; refraction by Hartinger coincidence refractometry and pupil diameter by vernier calipers) were recorded after anterior chamber exchange with (one eye) or without (opposite eye), muscarinic receptor subtype antagonist (pirenzepine, AF-DX 116 or 4-DAMP) [37].
  • Three Holstein steers (345 +/- 22 kg) surgically fitted with a pancreatic cannula were used in two 3 x 3 Latin square design experiments to examine the effects of slaframine (SF), a muscarinic agonist, or 4-diphenylacetoxy-N-methylpiperidine methiodide (4DAMP), an M3 muscarinic glandular receptor antagonist, on pancreatic exocrine secretion [38].


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  15. Functional role of muscarinic M(2) receptors in alpha,beta-methylene ATP induced, neurogenic contractions in guinea-pig ileum. Sawyer, G.W., Lambrecht, G., Ehlert, F.J. Br. J. Pharmacol. (2000) [Pubmed]
  16. Conversion of N-(2-chloroethyl)-4-piperidinyl diphenylacetate (4-DAMP mustard) to an aziridinium ion and its interaction with muscarinic receptors in various tissues. Thomas, E.A., Hsu, H.H., Griffin, M.T., Hunter, A.L., Luong, T., Ehlert, F.J. Mol. Pharmacol. (1992) [Pubmed]
  17. Receptor-coupled phosphoinositide hydrolysis in human retinal pigment epithelium. Feldman, E.L., Randolph, A.E., Johnston, G.C., DelMonte, M.A., Greene, D.A. J. Neurochem. (1991) [Pubmed]
  18. Characterization of the muscarinic receptors in the mesenteric vascular bed of spontaneously hypertensive rats. Hendriks, M.G., Pfaffendorf, M., van Zwieten, P.A. J. Hypertens. (1993) [Pubmed]
  19. Muscarinic receptor subtypes in human nasal mucosa: characterization, autoradiographic localization, and function in vitro. Okayama, M., Mullol, J., Baraniuk, J.N., Hausfeld, J.N., Feldman, B., Merida, M., Shelhamer, J.H., Kaliner, M.A. Am. J. Respir. Cell Mol. Biol. (1993) [Pubmed]
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  21. Drosophila nervous system muscarinic acetylcholine receptor: transient functional expression and localization by immunocytochemistry. Blake, A.D., Anthony, N.M., Chen, H.H., Harrison, J.B., Nathanson, N.M., Sattelle, D.B. Mol. Pharmacol. (1993) [Pubmed]
  22. Evidence for prejunctional muscarinic autoreceptors in human and guinea pig trachea. Patel, H.J., Barnes, P.J., Takahashi, T., Tadjkarimi, S., Yacoub, M.H., Belvisi, M.G. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  23. Characterization of the muscarinic receptor subtype involved in phosphoinositide metabolism in bovine tracheal smooth muscle. Roffel, A.F., Meurs, H., Elzinga, C.R., Zaagsma, J. Br. J. Pharmacol. (1990) [Pubmed]
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  26. Presynaptic dopamine D2 and muscarine M3 receptors inhibit excitatory and inhibitory transmission to rat subthalamic neurones in vitro. Shen, K.Z., Johnson, S.W. J. Physiol. (Lond.) (2000) [Pubmed]
  27. Histamine innervation and activation of septohippocampal GABAergic neurones: involvement of local ACh release. Xu, C., Michelsen, K.A., Wu, M., Morozova, E., Panula, P., Alreja, M. J. Physiol. (Lond.) (2004) [Pubmed]
  28. Change in muscarinic modulation of transmitter release in the rat urinary bladder after spinal cord injury. Somogyi, G.T., Zernova, G.V., Yoshiyama, M., Rocha, J.N., Smith, C.P., de Groat, W.C. Neurochem. Int. (2003) [Pubmed]
  29. Intrathecal clonidine inhibits mechanical allodynia via activation of the spinal muscarinic M1 receptor in streptozotocin-induced diabetic mice. Koga, K., Honda, K., Ando, S., Harasawa, I., Kamiya, H.O., Takano, Y. Eur. J. Pharmacol. (2004) [Pubmed]
  30. Extracellular signal regulated protein kinase and c-jun N-terminal kinase are involved in ml muscarinic receptor-enhanced interleukin-2 production pathway in Jurkat cells. Fujino, H., Uehara, T., Murayama, T., Okuma, Y., Ariga, H., Nomura, Y. Biol. Pharm. Bull. (2000) [Pubmed]
  31. The M2 muscarinic receptor mediates contraction through indirect mechanisms in mouse urinary bladder. Ehlert, F.J., Griffin, M.T., Abe, D.M., Vo, T.H., Taketo, M.M., Manabe, T., Matsui, M. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  32. Expression of muscarinic M3-receptors coupled to inositol phospholipid hydrolysis in human detrusor cultured smooth muscle cells. Harriss, D.R., Marsh, K.A., Birmingham, A.T., Hill, S.J. J. Urol. (1995) [Pubmed]
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