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Chemical Compound Review

Serotonin 5-HT2 Receptor Antagonists     (2,3-dimethoxyphenyl)-[1-[2- (4...

Synonyms: AGN-PC-00INZS, SureCN340674, CHEBI:537588, AC1Q4NRW, MDL-100,907, ...
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Disease relevance of M100907

  • OBJECTIVES: The present studies examined the ability of the selective 5-HT(2A)R antagonist M100907 to block hyperactivity and hyperthermia produced across the (+)-MDMA dose-effect curve [1].
  • Neither MDL 100,907 nor clozapine reduced apomorphine-induced stereotypies or produced catalepsy in rats [2].
  • Since l-DOPA induced dyskinesia (LID) may be mediated by oversensitive D1-mediated signaling, the present study examined the effects of the selective 5-HT2A antagonist M100907 on LID behaviors in DA-depleted rats [3].
  • Similarly, SB 206553 was more effective than MDL 100,907 in reducing the DOI-induced increase in lordosis responding [4].

Psychiatry related information on M100907


High impact information on M100907

  • 5-HT2A receptor antagonists (including MDL-100907 and cyproheptadine (CYP)) were found to inhibit 5-HT-induced, but not eotaxin-induced migration [8].
  • Twelve control studies and four preblocking studies (400 nmol/kg unlabeled MDL 100,907) were performed in isoflurane-anesthetized rhesus monkeys [9].
  • METHODS: Using CAR behavior, in a conventional shuttle-box paradigm, as an index for antipsychotic efficacy, the effects of the selective serotonin2A receptor antagonist MDL 100,907 alone, and in combination with the dopamine D2 receptor antagonist raclopride, were studied in adult male Sprague-Dawley rats [10].
  • Impairments in attentional functioning induced by CPP were completely abolished by both doses of 8-OH-DPAT or M100907 [11].
  • Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice [12].

Biological context of M100907


Anatomical context of M100907


Associations of M100907 with other chemical compounds

  • The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice [12].
  • Furthermore, the atypical APD clozapine, but not the typical APD haloperidol or raclopride (a selective dopamine D2,3 receptor antagonist), mimicked the action of M100907, preventing the PCP-induced effect [23].
  • Intrastriatal infusions of the selective 5-HT2 antagonist MDL 100,907 produced a concentration-dependent inhibition of MDMA-induced dopamine release [24].
  • In addition, M100907 (5-HT2A antagonist) but not SB-242084 (5-HT2C antagonist) reversed the cirazoline- and AMPA-induced 5-HT release [25].
  • 3. Clozapine (0.2 mg kg(-1) s.c. ), GYKI 53655 (5 mg kg(-1) i.p.), prazosin (0.05 and 0.1 mg kg(-1) i.p.), and M100907 (0.01 and 0.05 mg kg(-1) s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg(-1) s.c.), but not the increase in power at 1 - 3 Hz in prefrontal cortex [26].

Gene context of M100907

  • Furthermore, to determine which serotonergic receptor subtype may mediate this effect, the 5-HT2A receptor antagonist M100907 (formerly MDL 100,907) and the 5-HT2C receptor antagonist SDZ SER 082 were tested against dizocilpine [27].
  • M100907, a selective 5-HT2A receptor antagonist and a potential antipsychotic drug, facilitates N-methyl-D-aspartate-receptor mediated neurotransmission in the rat medial prefrontal cortical neurons in vitro [13].
  • Electrophysiological, biochemical and behavioral evidence obtained using highly selective antagonists of the 5-HT2 or 5-HT3 receptor subtypes, MDL 100,907 or MDL 73,147EF, respectively, supports the thesis that serotonin modulates the dopaminergic system [28].
  • Because l-DOPA induced AIMs in rats are dependent upon D1 and D2 receptor activation, a second study was performed to determine if M100907 could suppress D1- or D2-mediated rotational behaviors [3].
  • We hypothesize that the ability of M100907 and clozapine to prevent or reverse the PCP-induced blockade of the NMDA receptor channel is attributed to their 5-HT2A receptors antagonizing property [23].

Analytical, diagnostic and therapeutic context of M100907

  • Time course of 5-HT2A receptor occupancy in the human brain after a single oral dose of the putative antipsychotic drug MDL 100,907 measured by positron emission tomography [29].
  • Plasma concentrations of MDL 100,907 were measured with high-pressure liquid chromatography [19].
  • The 5-HT(2A)-antagonist, M100907, specifically increased EEG power at 2 - 3 Hz at low doses (10 and 50 microg kg(-1) s.c.), whereas at higher doses (0.1 mg kg(-1) s.c.) the profile resembled that of clozapine [26].
  • With these data, clear go/no-go decision points could be established early within the clinical drug development process, and the selection of M100907 doses to carry forward into large-scale clinical trials in patients with schizophrenia could be narrowed [30].
  • Investigation of the CNS penetration of a potent 5-HT2a receptor antagonist (MDL 100,907) and an active metabolite (MDL 105,725) using in vivo microdialysis sampling in the rat [31].


  1. Role of the serotonin 5-HT2A receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine. Herin, D.V., Liu, S., Ullrich, T., Rice, K.C., Cunningham, K.A. Psychopharmacology (Berl.) (2005) [Pubmed]
  2. Characterization of the 5-HT2 receptor antagonist MDL 100907 as a putative atypical antipsychotic: behavioral, electrophysiological and neurochemical studies. Sorensen, S.M., Kehne, J.H., Fadayel, G.M., Humphreys, T.M., Ketteler, H.J., Sullivan, C.K., Taylor, V.L., Schmidt, C.J. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  3. Serotonin 2A receptor antagonist treatment reduces dopamine D1 receptor-mediated rotational behavior but not l-DOPA-induced abnormal involuntary movements in the unilateral dopamine-depleted rat. Taylor, J.L., Bishop, C., Ullrich, T., Rice, K.C., Walker, P.D. Neuropharmacology (2006) [Pubmed]
  4. 5-HT2C receptor involvement in female rat lordosis behavior. Wolf, A., Caldarola-Pastuszka, M., DeLashaw, M., Uphouse, L. Brain Res. (1999) [Pubmed]
  5. Intra-prefrontal 8-OH-DPAT and M100907 improve visuospatial attention and decrease impulsivity on the five-choice serial reaction time task in rats. Winstanley, C.A., Chudasama, Y., Dalley, J.W., Theobald, D.E., Glennon, J.C., Robbins, T.W. Psychopharmacology (Berl.) (2003) [Pubmed]
  6. Reversal of amphetamine-induced behaviours by MDL 100,907, a selective 5-HT2A antagonist. Moser, P.C., Moran, P.M., Frank, R.A., Kehne, J.H. Behav. Brain Res. (1996) [Pubmed]
  7. Mixed D2/5-HT2 antagonism differentially affects apomorphine- and amphetamine-induced stereotyped behavior. Feldman, D.J., Frank, R.A., Kehne, J.H., Flannery, R., Brown, D., Soni, S., Byrd, G., Shah, S. Pharmacol. Biochem. Behav. (1997) [Pubmed]
  8. Cutting edge: serotonin is a chemotactic factor for eosinophils and functions additively with eotaxin. Boehme, S.A., Lio, F.M., Sikora, L., Pandit, T.S., Lavrador, K., Rao, S.P., Sriramarao, P. J. Immunol. (2004) [Pubmed]
  9. Kinetic analysis of the 5-HT2A ligand [11C]MDL 100,907. Watabe, H., Channing, M.A., Der, M.G., Adams, H.R., Jagoda, E., Herscovitch, P., Eckelman, W.C., Carson, R.E. J. Cereb. Blood Flow Metab. (2000) [Pubmed]
  10. Enhancement of antipsychoticlike properties of raclopride in rats using the selective serotonin2A receptor antagonist MDL 100,907. Wadenberg, M.L., Hicks, P.B., Richter, J.T., Young, K.A. Biol. Psychiatry (1998) [Pubmed]
  11. Dissociable contribution of 5-HT1A and 5-HT2A receptors in the medial prefrontal cortex to different aspects of executive control such as impulsivity and compulsive perseveration in rats. Carli, M., Baviera, M., Invernizzi, R.W., Balducci, C. Neuropsychopharmacology (2006) [Pubmed]
  12. The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice. Barr, A.M., Lehmann-Masten, V., Paulus, M., Gainetdinov, R.R., Caron, M.G., Geyer, M.A. Neuropsychopharmacology (2004) [Pubmed]
  13. M100907, a selective 5-HT2A receptor antagonist and a potential antipsychotic drug, facilitates N-methyl-D-aspartate-receptor mediated neurotransmission in the rat medial prefrontal cortical neurons in vitro. Arvanov, V.L., Wang, R.Y. Neuropsychopharmacology (1998) [Pubmed]
  14. M100907, a highly selective 5-HT2A receptor antagonist and a potential atypical antipsychotic drug, facilitates induction of long-term potentiation in area CA1 of the rat hippocampal slice. Wang, R.Y., Arvanov, V.L. Brain Res. (1998) [Pubmed]
  15. 5-HT2C receptors mediate penile erections in rats: actions of novel and selective agonists and antagonists. Millan, M.J., Peglion, J.L., Lavielle, G., Perrin-Monneyron, S. Eur. J. Pharmacol. (1997) [Pubmed]
  16. 5-HT2A and 5-HT2C/5-HT1B receptors are differentially involved in alcohol preference and consummatory behavior in cAA rats. Maurel, S., De Vry, J., De Beun, R., Schreiber, R. Pharmacol. Biochem. Behav. (1999) [Pubmed]
  17. Modulation of brainstem 5-HT1C receptors by serotonergic drugs in the rat. Pranzatelli, M.R., Tailor, P.T. Gen. Pharmacol. (1994) [Pubmed]
  18. SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Bonaccorso, S., Meltzer, H.Y., Li, Z., Dai, J., Alboszta, A.R., Ichikawa, J. Neuropsychopharmacology (2002) [Pubmed]
  19. Positron emission tomographic analysis of dose-dependent MDL 100,907 binding to 5-hydroxytryptamine-2A receptors in the human brain. Andrée, B., Nyberg, S., Ito, H., Ginovart, N., Brunner, F., Jaquet, F., Halldin, C., Farde, L. Journal of clinical psychopharmacology. (1998) [Pubmed]
  20. Regional effects of MK-801 on dopamine release: effects of competitive NMDA or 5-HT2A receptor blockade. Schmidt, C.J., Fadayel, G.M. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  21. Extracellular single-unit recordings of piriform cortex neurons in rats: influence of different types of anesthesia and characterization of neurons by pharmacological manipulation of serotonin receptors. Bloms-Funke, P., Gernert, M., Ebert, U., Löscher, W. J. Neurosci. Res. (1999) [Pubmed]
  22. Clozapine and other 5-hydroxytryptamine-2A receptor antagonists alter the subcellular distribution of 5-hydroxytryptamine-2A receptors in vitro and in vivo. Willins, D.L., Berry, S.A., Alsayegh, L., Backstrom, J.R., Sanders-Bush, E., Friedman, L., Roth, B.L. Neuroscience (1999) [Pubmed]
  23. M100907 and clozapine, but not haloperidol or raclopride, prevent phencyclidine-induced blockade of NMDA responses in pyramidal neurons of the rat medial prefrontal cortical slice. Wang, R.Y., Liang, X. Neuropsychopharmacology (1998) [Pubmed]
  24. Blockade of striatal 5-hydroxytryptamine2 receptors reduces the increase in extracellular concentrations of dopamine produced by the amphetamine analogue 3,4-methylenedioxymethamphetamine. Schmidt, C.J., Sullivan, C.K., Fadayel, G.M. J. Neurochem. (1994) [Pubmed]
  25. Stimulation of alpha1-adrenoceptors in the rat medial prefrontal cortex increases the local in vivo 5-hydroxytryptamine release: reversal by antipsychotic drugs. Amargós-Bosch, M., Adell, A., Bortolozzi, A., Artigas, F. J. Neurochem. (2003) [Pubmed]
  26. Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, alpha(1)- and 5-HT(2A)-receptors. Sebban, C., Tesolin-Decros, B., Ciprian-Ollivier, J., Perret, L., Spedding, M. Br. J. Pharmacol. (2002) [Pubmed]
  27. M100907, a serotonin 5-HT2A receptor antagonist and putative antipsychotic, blocks dizocilpine-induced prepulse inhibition deficits in Sprague-Dawley and Wistar rats. Varty, G.B., Bakshi, V.P., Geyer, M.A. Neuropsychopharmacology (1999) [Pubmed]
  28. Electrophysiological, biochemical and behavioral evidence for 5-HT2 and 5-HT3 mediated control of dopaminergic function. Palfreyman, M.G., Schmidt, C.J., Sorensen, S.M., Dudley, M.W., Kehne, J.H., Moser, P., Gittos, M.W., Carr, A.A. Psychopharmacology (Berl.) (1993) [Pubmed]
  29. Time course of 5-HT2A receptor occupancy in the human brain after a single oral dose of the putative antipsychotic drug MDL 100,907 measured by positron emission tomography. Gründer, G., Yokoi, F., Offord, S.J., Ravert, H.T., Dannals, R.F., Salzmann, J.K., Szymanski, S., Wilson, P.D., Howard, D.R., Wong, D.F. Neuropsychopharmacology (1997) [Pubmed]
  30. The role of positron emission tomography in the drug development of M100907, a putative antipsychotic with a novel mechanism of action. Offord, S.J., Wong, D.F., Nyberg, S. Journal of clinical pharmacology. (1999) [Pubmed]
  31. Investigation of the CNS penetration of a potent 5-HT2a receptor antagonist (MDL 100,907) and an active metabolite (MDL 105,725) using in vivo microdialysis sampling in the rat. Scott, D.O., Heath, T.G. Journal of pharmaceutical and biomedical analysis. (1998) [Pubmed]
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