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Chemical Compound Review

AG-J-63698     (8-methyl-8- azabicyclo[3.2.1]oct-3-yl) 3,5...

Synonyms: SureCN5790539, MDL-72222, MDL-72699, CHEBI:473376, CCG-205296, ...
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Disease relevance of MDL 72222


Psychiatry related information on MDL 72222


High impact information on MDL 72222

  • Recently, GR38032F, MDL 72222 and ICS 205-930 have been shown to have behavioural effects in rodents and primates that undoubtedly reflect an action in the central nervous system (refs 9-11 and unpublished observations), suggesting the existence of 5-HT3 receptors in the brain [8].
  • Membranes from transfected cells showed high-affinity binding of the serotonin antagonists spiperone, ketanserin and mianserin, low affinity for haloperidol (a dopamine D2 receptor antagonist), 8-OH-DPAT as well as MDL-72222 and no detectable binding of [3H]serotonin [9].
  • Binding of [3H]5-HT to enteric membranes is inhibited by 5-HT1P receptor agonists and antagonists but not by the 5-HT2P receptor antagonist ICS 205-930 or by MDL 72222, another compound reported to be an antagonist of 5-HT at peripheral receptors [10].
  • Our results suggest that MDL 72222 attenuates MAP-induced behavioral sensitization via 5-HT(3) receptors in the caudate putamen, and that 5-HT(3) receptor antagonists like MDL 72222 have potential as novel anti-psychotic agents for the treatment of MAP dependence and psychosis [11].
  • The depolarizing response was mimicked by the 5-HT2 receptor agonist (+2-)-1(2,5-dimethyoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) and blocked by 5-HT antagonists methysergide and cyproheptadine and by 5-HT2 antagonists ketanserin and spiperone; methiothepin and MDL 72222 were without effect [12].

Chemical compound and disease context of MDL 72222


Biological context of MDL 72222


Anatomical context of MDL 72222

  • Thus, in the neuronal cell line cytosolic Ca2+ activity is raised through enhancement of Ca2+ entry into the cells from the extracellular environment via 5-HT3 receptors (blocked by ICS 205-930, MDL 72222 and GR 38032 F) [18].
  • Quipazine, MDL 72222 and ICS 205-930 were also shown to be effective antagonists of 5-HT on the vagus nerve [19].
  • Apparent pA2 values were determined from individual experiments on both the nodose and superior cervical ganglia, where MDL 72222 (10(-7) M or less, for 1 hr) caused parallel or near parallel shifts of dose-response curves [20].
  • In the nodose ganglion, after equilibration for 1 hr with 10(-8) or 10(-7) M MDL 72222, dose-response curves for 5-HT showed rightward, parallel shifts [20].
  • The facilitations of the ventral root potentials were blocked by the serotonin1A antagonist spiroxatrine, but were unaffected by the serotonin2 antagonist ketanserin or the serotonin3 antagonist 1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,-dichlorobenzoate (MDL 72222) [21].

Associations of MDL 72222 with other chemical compounds


Gene context of MDL 72222


Analytical, diagnostic and therapeutic context of MDL 72222

  • The channel activity induced by bath perfusion of 5-HT (0.8 microM) was significantly reduced by 100 nM of the 5-HT3 receptor-specific antagonists 3-tropanyl-3,5-dichlorobenzoate (MDL 72222) or 3-tropanyl-indole-3-carboxylate (ICS 205-930) [32].
  • Both MDL 72222 and MDL 73147EF produced flat dose-response curves, with significant inhibition of defensive analgesia at minimum effective doses of less than or equal to 10 and 300 micrograms/kg, respectively [29].
  • Intrathecal injection of the 5-HT(2) receptor antagonist RS 102221 and the 5-HT(3) receptor antagonist MDL 72222 had no significant effects on the increased hindpaw withdrawal latencies to both noxious stimulations induced by intra-periaqueductal gray injection of morphine [33].
  • Intravenous injection of the 5-HT3 antagonist MDL 72222 (1.0 mg kg-1) markedly attenuated the responses to phenylbiguanide.(ABSTRACT TRUNCATED AT 250 WORDS)[34]
  • The drug MDL 72222, a selective 5-HT3 receptor antagonist, was labelled with 11C and evaluated for distribution kinetics in brain and in vivo binding to 5-HT3 receptors using cold MDL 72222 challenge and positron emission tomography (PET), in three anaesthetized baboons [14].


  1. Effects of 5-HT3 receptor antagonists on neuroleptic-induced catalepsy in mice. Silva, S.R., Futuro-Neto, H.A., Pires, J.G. Neuropharmacology (1995) [Pubmed]
  2. Temperature, food intake, and locomotor activity effects of a 5-HT3 receptor agonist and two 5-HT3 receptor antagonists in rats. Mazzola-Pomietto, P., Aulakh, C.S., Murphy, D.L. Psychopharmacology (Berl.) (1995) [Pubmed]
  3. Effects of the antagonists MDL 72222 and ketanserin on responses of cat carotid body chemoreceptors to 5-hydroxytryptamine. Kirby, G.C., McQueen, D.S. Br. J. Pharmacol. (1984) [Pubmed]
  4. 5-Hydroxytryptamine mediates the post-embolic increase in respiratory rate in anaesthetized rabbits. Armstrong, D.J., Kay, I.S. Exp. Physiol. (1990) [Pubmed]
  5. Effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on 5-HTP-induced head shaking and behavioral symptoms induced by 5-methoxy-N,N,dimethyltryptamine in rats: comparison with some other 5-HT receptor antagonists. Shearman, G.T., Tolcsvai, L. Psychopharmacology (Berl.) (1987) [Pubmed]
  6. The pharmacology of impulsive behaviour in rats VII: the effects of serotonergic agonists and antagonists on responding under a discrimination task using unreliable visual stimuli. Evenden, J.L. Psychopharmacology (Berl.) (1999) [Pubmed]
  7. The effects of selective activation of the 5-HT3 receptor with m-chlorophenylbiguanide on sleep and wakefulness in the rat. Ponzoni, A., Monti, J.M., Jantos, H. Eur. J. Pharmacol. (1993) [Pubmed]
  8. Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Kilpatrick, G.J., Jones, B.J., Tyers, M.B. Nature (1987) [Pubmed]
  9. Structure and functional expression of cloned rat serotonin 5HT-2 receptor. Pritchett, D.B., Bach, A.W., Wozny, M., Taleb, O., Dal Toso, R., Shih, J.C., Seeburg, P.H. EMBO J. (1988) [Pubmed]
  10. Peripheral neural serotonin receptors: identification and characterization with specific antagonists and agonists. Mawe, G.M., Branchek, T.A., Gershon, M.D. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  11. Involvement of 5-HT receptors in the development and expression of methamphetamine-induced behavioral sensitization: 5-HT receptor channel and binding study. Yoo, J.H., Cho, J.H., Yu, H.S., Lee, K.W., Lee, B.H., Jeong, S.M., Nah, S.Y., Kim, H.C., Lee, S.Y., Jang, C.G. J. Neurochem. (2006) [Pubmed]
  12. 5-Hydroxytryptamine responses in neonate rat motoneurones in vitro. Wang, M.Y., Dun, N.J. J. Physiol. (Lond.) (1990) [Pubmed]
  13. Nicotine self-administration and locomotor activity are not modified by the 5-HT3 antagonists ICS 205-930 and MDL 72222. Corrigall, W.A., Coen, K.M. Pharmacol. Biochem. Behav. (1994) [Pubmed]
  14. Positron emission tomographic studies of [11C]MDL 72222, a potential 5-HT3 receptor radioligand: distribution, kinetics and binding in the brain of the baboon. Camsonne, R., Barre, L., Petit-Taboué, M.C., Travère, J.M., Jones, R., Debruyne, D., Moulin, M.A., MacKenzie, E.T., Baron, J.C. Neuropharmacology (1993) [Pubmed]
  15. The effects of 5-HT on articular sensory receptors in normal and arthritic rats. Birrell, G.J., McQueen, D.S., Iggo, A., Grubb, B.D. Br. J. Pharmacol. (1990) [Pubmed]
  16. The 5-HT3 receptor antagonist, MDL 72222, dose-dependently potentiates morphine-induced immediate-early gene expression in the rat caudate putamen. Frankel, P.S., Harlan, R.E., Garcia, M.M. Brain Res. (1998) [Pubmed]
  17. Characterisation of 5-HT3 recognition sites in membranes of NG 108-15 neuroblastoma-glioma cells with [3H]ICS 205-930. Neijt, H.C., Karpf, A., Schoeffter, P., Engel, G., Hoyer, D. Naunyn Schmiedebergs Arch. Pharmacol. (1988) [Pubmed]
  18. Serotonin regulates cytosolic Ca2+ activity and membrane potential in a neuronal and in a glial cell line via 5-HT3 and 5-HT2 receptors by different mechanisms. Reiser, G., Donié, F., Binmöller, F.J. J. Cell. Sci. (1989) [Pubmed]
  19. Pharmacological characterization of 5-hydroxytryptamine-induced depolarization of the rat isolated vagus nerve. Ireland, S.J., Tyers, M.B. Br. J. Pharmacol. (1987) [Pubmed]
  20. Further studies on the blockade of 5-HT depolarizations of rabbit vagal afferent and sympathetic ganglion cells by MDL 72222 and other antagonists. Round, A., Wallis, D.I. Neuropharmacology (1987) [Pubmed]
  21. Serotonin1A facilitation of frog motoneuron responses to afferent stimuli and to N-methyl-D-aspartate. Holohean, A.M., Hackman, J.C., Shope, S.B., Davidoff, R.A. Neuroscience (1992) [Pubmed]
  22. Investigation into the 5-hydroxytryptamine receptor mediating smooth muscle relaxation in the rat oesophagus. Reeves, J.J., Bunce, K.T., Humphrey, P.P. Br. J. Pharmacol. (1991) [Pubmed]
  23. 5HT3 receptor antagonists block morphine- and nicotine- but not amphetamine-induced reward. Carboni, E., Acquas, E., Leone, P., Di Chiara, G. Psychopharmacology (Berl.) (1989) [Pubmed]
  24. The discriminative stimulus effects of methamphetamine in pigeons. Sasaki, J.E., Tatham, T.A., Barrett, J.E. Psychopharmacology (Berl.) (1995) [Pubmed]
  25. Evidence that blockade of post-synaptic 5-HT1 receptors elicits feeding in satiated rats. Dourish, C.T., Clark, M.L., Fletcher, A., Iversen, S.D. Psychopharmacology (Berl.) (1989) [Pubmed]
  26. Serotonin induces the increase in intracellular Ca2+ that enhances neurite outgrowth in PC12 cells via activation of 5-HT3 receptors and voltage-gated calcium channels. Homma, K., Kitamura, Y., Ogawa, H., Oka, K. J. Neurosci. Res. (2006) [Pubmed]
  27. An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats. Sartor, D.M., Shulkes, A., Verberne, A.J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  28. Effects of 5-HT3 receptor antagonists on binding and function of mouse and human GABAA receptors. Klein, R.L., Sanna, E., McQuilkin, S.J., Whiting, P.J., Harris, R.A. Eur. J. Pharmacol. (1994) [Pubmed]
  29. Attenuation of defensive analgesia in male mice by 5-HT3 receptor antagonists, ICS 205-930, MDL 72222, MDL 73147EF and MDL 72699. Rodgers, R.J., Shepherd, J.K. Neuropharmacology (1992) [Pubmed]
  30. 5-Hydroxytryptamine modulation of electrically induced twitch responses of mouse vas deferens: involvement of multiple 5-hydroxytryptamine receptors. Seong, Y.H., Baba, A., Matsuda, T., Iwata, H. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
  31. Identification of 5-HT3 binding sites in rat spinal cord synaptosomal membranes. Glaum, S.R., Anderson, E.G. Eur. J. Pharmacol. (1988) [Pubmed]
  32. 5-HT3 receptor channels in dissociated rat superior cervical ganglion neurons. Yang, J., Mathie, A., Hille, B. J. Physiol. (Lond.) (1992) [Pubmed]
  33. Involvement of 5-hydroxytryptamine(1A) receptors in the descending anti-nociceptive pathway from periaqueductal gray to the spinal dorsal horn in intact rats, rats with nerve injury and rats with inflammation. Liu, Z.Y., Zhuang, D.B., Lunderberg, T., Yu, L.C. Neuroscience (2002) [Pubmed]
  34. Chemosensitive cardiopulmonary afferents and the haemodynamic response to simulated haemorrhage in conscious rabbits. Evans, R.G., Ludbrook, J. Br. J. Pharmacol. (1991) [Pubmed]
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