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Chemical Compound Review

Lopac-G-5793     N-[4-methoxy-3-(4- methylpiperazin-1...

Synonyms: Tocris-1477, CHEMBL15928, SureCN7795263, CHEBI:64114, ANW-62582, ...
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Disease relevance of GR 127935


Psychiatry related information on GR 127935

  • In wild-type mice, the 5-HT1B agonists CP 94253 (1-10 mg/kg, i.p.) and RU 24969 (0.25-2.0 mg/kg, i.p.) induced a dose-dependent reduction of paradoxical sleep during the 2-6 hr after injection, whereas the 5-HT1B/1D antagonist GR 127935 (0.1-1.0 mg/kg, i.p.) enhanced paradoxical sleep [2].
  • To confirm these findings, we tested the effects of MDMA on the locomotor and exploratory behavior of wild-type mice pretreated with GR 127935, a 5-HT1B/1D receptor antagonist [3].
  • Reduced locomotor activity following TFMPP was blocked by SB 242084 but not WAY 100635 (0.1 mg/kg s.c.) or GR 127935 (3.0 mg/kg s.c.). Behaviourally relevant levels of 5-HT2C receptor stimulation may not exert reinforcing effects, although other studies indicate that such manipulations alter reinforcing effects of drugs of abuse [4].

High impact information on GR 127935

  • Notably, SB-224289 at 1.0mg/kg potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist mixed GR 127935, which facilitated learning consolidation and this effect was abolished by ketanserin at a higher dose [5].
  • Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose) [5].
  • In addition, either the absence of the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiated the effect of a single administration of paroxetine on extracellular 5-HT levels more in the ventral hippocampus than in the frontal cortex [6].
  • In contrast, the mixed 5-HT1B/1D receptor antagonist GR-127935 exhibited equal affinity for both isoforms [7].
  • SB-224289, which decreased [35S]GTPgammaS binding when given alone, but not GR-127935, was more potent in antagonizing the stimulatory effect of 5-CT on [35S]GTPgammaS binding to membranes expressing the VR compared to membranes expressing the WTR [7].

Biological context of GR 127935


Anatomical context of GR 127935


Associations of GR 127935 with other chemical compounds

  • However, pretreatment with an intermediate dose of GR 127935 (3 mg/kg), which was previously without effect on ICSS behavior, reversed the threshold-elevating effects of RU 24969 (1 mg/kg), suggesting the involvement of the 5-HT1B receptor in this effect of RU 24969 administration [14].
  • The response pattern to fluoxetine alone in 5-HT receptor mutant mice corresponded with the effects of fluoxetine given with either the 5-HT(1A) receptor antagonist WAY 100635 (0.1 mg/kg i.p.) or the 5-HT(1B/1D) receptor antagonist GR 127935 (0.056 mg/kg) in wild-type mice [15].
  • Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1D receptor antagonist [16].
  • The reduction in aggression was antagonized by GR 127935, indicated by a rightward shift in the dose-effect curves of zolmitriptan, showing the specificity for the 5-HT1B receptors [17].
  • In addition, the discriminative stimulus produced by CP-135,807 was not blocked by WAY 100,635, a selective 5-HT1A antagonist, but was completely and dose-dependently antagonized by the selective 5-HT1D antagonist, GR 127935 [18].

Gene context of GR 127935

  • Metergoline and the selective 5-HT 1B/D receptor ligands GR 127935 as well as GR 125743 showed significant intrinsic activity (43% to 69%) at the 5-HT 1D receptor subtype, whereas the nonselective ligand 1-naphthylpiperazine yielded less (15% to 19%) intrinsic activity at both receptor subtypes [19].
  • Furthermore, the hyperlocomotion produced by m-CPP in the presence of LY53857 (1.0 mg/kg) was blocked by both the 5-HT(1B/1D) receptor antagonist GR 127935 (3.0 mg/kg) and the 5-HT1A receptor antagonist WAY 100,635 (1.0 mg/kg) [20].
  • The inhibitory effect of 5-CT was blocked by the 5-HT1/2 antagonist methiothepin (1 microM), the 5-HT1A antagonist S-UH-301 (1 microM), and the 5-HT1B/1D antagonist GR 127935 (1 microM) [21].
  • GR 127935 (1 mg/kg, s.c.), SB 200646A (without effect per se at 10 mg/kg, s.c.) and MDL 100,151 (0.3 mg/kg, s.c.) did not inhibit the cataleptic response to the dopamine D2 receptor antagonist, loxapine (0.3 mg/kg, s.c [22].
  • 5-HT7 binding sites were labelled in rat and guinea pig brains by incubating with 3H-5-CT in the presence of 100 microM WAY 100135 and 250 microM GR 127935; the distribution obtained in both species agreed, in general, with that of the corresponding mRNA coding for them [23].

Analytical, diagnostic and therapeutic context of GR 127935

  • On the other hand, PA constriction to 5-HT was attenuated by either the addition of GR-127935 (0.1 microM, a selective inhibitor of 5-HT(1B/1D) receptor) or copper/zinc-containing superoxide dismutase (Cu/Zn SOD, 150 U/ml) and in PA isolated from transgenic mice overexpressing human EC-SOD [24].
  • In vivo, using the technique of microdialysis, GR 127935 and the non-selective antagonist methiothepin, when administered down the dialysis probe, potentiate extracellular levels of 5-HT [13].


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  3. Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor. Scearce-Levie, K., Viswanathan, S.S., Hen, R. Psychopharmacology (Berl.) (1999) [Pubmed]
  4. Differential effects of 5-HT2C receptor ligands on place conditioning and locomotor activity in rats. Mosher, T., Hayes, D., Greenshaw, A. Eur. J. Pharmacol. (2005) [Pubmed]
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  8. Radioligand binding analysis of knockout mice reveals 5-hydroxytryptamine(7) receptor distribution and uncovers 8-hydroxy-2-(di-n-propylamino)tetralin interaction with alpha(2) adrenergic receptors. Bonaventure, P., Nepomuceno, D., Hein, L., Sutcliffe, J.G., Lovenberg, T., Hedlund, P.B. Neuroscience (2004) [Pubmed]
  9. Donitriptan selectively decreases jugular venous oxygen saturation in the anesthetized pig: further insights into its mechanism of action relevant to headache relief. Letienne, R., Verscheure, Y., Perez, M., Le Grand, B., Colpaert, F.C., John, G.W. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  10. Autoradiographic characterisation of [35S]GTPgammaS binding stimulation mediated by 5-HT1B receptor in postmortem human brain. Mostany, R., Pazos, A., Castro, M.E. Neuropharmacology (2005) [Pubmed]
  11. Serotonergic modulation of murine fundic tone. Xue, L., Camilleri, M., Locke, G.R., Schuurkes, J.A., Meulemans, A., Coulie, B.J., Szurszewski, J.H., Farrugia, G. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  12. Differential effects of 5-HT1B/1D receptor antagonists in dorsal and median raphe innervated brain regions. Roberts, C., Belenguer, A., Middlemiss, D.N., Routledge, C. Eur. J. Pharmacol. (1998) [Pubmed]
  13. Species differences in 5-HT autoreceptors. Price, G.W., Roberts, C., Watson, J., Burton, M., Mulholland, K., Middlemiss, D.N., Jones, B.J. Behav. Brain Res. (1996) [Pubmed]
  14. RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist. Harrison, A.A., Parsons, L.H., Koob, G.F., Markou, A. Psychopharmacology (Berl.) (1999) [Pubmed]
  15. Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse. Knobelman, D.A., Hen, R., Lucki, I. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  16. Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1D receptor antagonist. De Vries, P., Heiligers, J.P., Villalón, C.M., Saxena, P.R. Br. J. Pharmacol. (1996) [Pubmed]
  17. Zolmitriptan--a 5-HT1B/D agonist, alcohol, and aggression in mice. de Almeida, R.M., Nikulina, E.M., Faccidomo, S., Fish, E.W., Miczek, K.A. Psychopharmacology (Berl.) (2001) [Pubmed]
  18. CP-135,807, a selective 5-HT1D agonist: effects in drug discrimination and punishment procedures in the pigeon. Mansbach, R.S., Rovetti, C.C., Macor, J.E. Psychopharmacology (Berl.) (1996) [Pubmed]
  19. 5-HT 1B/D receptor antagonists. Pauwels, P.J. Gen. Pharmacol. (1997) [Pubmed]
  20. Meta-chlorophenylpiperazine induced changes in locomotor activity are mediated by 5-HT1 as well as 5-HT2C receptors in mice. Gleason, S.D., Shannon, H.E. Eur. J. Pharmacol. (1998) [Pubmed]
  21. 5-HT1D receptors regulate 5-HT release in the rat raphe nuclei. In vivo voltammetry and in vitro superfusion studies. Piñeyro, G., de Montigny, C., Blier, P. Neuropsychopharmacology (1995) [Pubmed]
  22. Cataleptogenic effect of subtype selective 5-HT receptor antagonists in the rat. Kalkman, H.O., Neumann, V., Nozulak, J., Tricklebank, M.D. Eur. J. Pharmacol. (1998) [Pubmed]
  23. 5-HT receptors in mammalian brain: receptor autoradiography and in situ hybridization studies of new ligands and newly identified receptors. Mengod, G., Vilaró, M.T., Raurich, A., López-Giménez, J.F., Cortés, R., Palacios, J.M. Histochem. J. (1996) [Pubmed]
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