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Chemical Compound Review

Loreclezol     1-[(Z)-2-chloro-2-(2,4...

Synonyms: Loreclezole, Loreclezolum, Tocris-1295, AC1MHWQV, CHEMBL1397886, ...
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Disease relevance of R 72063


Psychiatry related information on R 72063


High impact information on R 72063


Biological context of R 72063


Anatomical context of R 72063

  • We used patch-clamp recording from outside-out and inside-out patches from L929 fibroblasts transiently transfected with rat GABAR subunits to examine the properties of inhibition of alpha1beta1gamma2L single channel currents by loreclezole [12].
  • 4. In the [3H]-FNZ binding studies on well-washed membranes, loreclezole enhanced binding to a maximum of 47.3 +/- 2.83% of control (mean +/- s.e.mean, n = 3) at 300 microM [13].
  • The recurrent discharges in the entorhinal cortex were reliably blocked by 80 microM loreclezole applied for 80-100 min [14].
  • The recurrent short discharges in the hippocampus were reliably blocked by 40 muM loreclezole 60-90 min after bath application with incomplete recovery after washout of several hours [14].
  • The rapid onset of activity indicates that loreclezole readily passes the blood-brain barrier [15].

Associations of R 72063 with other chemical compounds

  • We were interested to know how receptors containing both beta1 and beta2 subunits, in different positions respond to loreclezole and etomidate [16].
  • Thymol (1-100 microm) potentiation of responses to EC20 GABA for alpha1beta1gamma2s, alpha6beta3gamma2s and alpha1beta3gamma2s human GABAA receptors was almost identical, arguing against actions at benzodiazepine or loreclezole sites [17].
  • These data suggest that loreclezole shares, with propofol, an agonistic action at GABAA receptors containing the beta 2-subunit and that the different efficacies of the two compounds in this regard, may underlie the difference in their pharmacological profiles [18].
  • A number of drugs presently under development, such as NMDA receptor antagonists, loreclezole, losigamone, methysticine, and dextromethorphan, are promising in acute animal models of otherwise drug-resistant convulsant activity [19].
  • Diflunisal was the most efficacious compound, eliciting greater potentiation than loreclezole (90 +/- 14% and 109 +/- 14% at beta3 and beta2, respectively, compared with 62 +/- 6% and 56 +/- 3%), whereas niflumic acid exhibited the lowest efficacy [20].

Gene context of R 72063

  • By mutating single amino acids of the beta 1 subunit to the beta 2/beta 3 equivalent, only the beta 1 mutation of Ser-290-->Asn conferred potentiation by loreclezole [7].
  • Loreclezole enhances apparent desensitization of recombinant GABAA receptor currents [21].
  • It has been known that neurosteroids and barbiturates are uniformly active in both the two subunit receptors, substituted pyrazinones are only active in the alpha 1 beta 2 subtype and loreclezole is active in the subtypes containing beta 2 [22].
  • Thirteen drug-resistant epilepsy patients received loreclezole as add-on therapy [23].
  • The effects of loreclezole and La3+ on native cerebellar GABA(A) receptors were compared between GABA(A) receptor alpha6 subunit-deficient (alpha6-/-) and wildtype mouse lines, produced through homologous recombination, using t-[35S]butylbicyclophosphorothionate ([35S]TBPS) autoradiography in brain sections [24].

Analytical, diagnostic and therapeutic context of R 72063

  • In addition, the effects of 0, 5, 10 and 20 mg/kg loreclezole on the spectral content of the background EEG and on spontaneous behaviour of rats were investigated [1].


  1. Effects of loreclezole on epileptic activity and on EEG and behaviour in rats with absence seizures. Ates, N., van Luijtelaar, E.L., Drinkenburg, W.H., Vossen, J.M., Coenen, A.M. Epilepsy Res. (1992) [Pubmed]
  2. In vivo studies on the mechanism of action of the broad spectrum anticonvulsant loreclezole. Ashton, D., Fransen, J., Heeres, J., Clincke, G.H., Janssen, P.A. Epilepsy Res. (1992) [Pubmed]
  3. Effects of loreclezole on metrazol-induced phenomena in developing rats. Pohl, M., Mares, P. Archives internationales de pharmacodynamie et de thérapie. (1990) [Pubmed]
  4. The role of GABAbeta2 subunit-containing receptors in mediating the anticonvulsant and sedative effects of loreclezole. Groves, J.O., Guscott, M.R., Hallett, D.J., Rosahl, T.W., Pike, A., Davies, A., Wafford, K.A., Reynolds, D.S. Eur. J. Neurosci. (2006) [Pubmed]
  5. Isobolographic analysis of interactions between loreclezole and conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Luszczki, J.J., Ratnaraj, N., Patsalos, P.N., Czuczwar, S.J. Naunyn Schmiedebergs Arch. Pharmacol. (2006) [Pubmed]
  6. A novel allosteric modulatory site on the GABAA receptor beta subunit. Wafford, K.A., Bain, C.J., Quirk, K., McKernan, R.M., Wingrove, P.B., Whiting, P.J., Kemp, J.A. Neuron (1994) [Pubmed]
  7. The modulatory action of loreclezole at the gamma-aminobutyric acid type A receptor is determined by a single amino acid in the beta 2 and beta 3 subunit. Wingrove, P.B., Wafford, K.A., Bain, C., Whiting, P.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux. Smith, A.J., Alder, L., Silk, J., Adkins, C., Fletcher, A.E., Scales, T., Kerby, J., Marshall, G., Wafford, K.A., McKernan, R.M., Atack, J.R. Mol. Pharmacol. (2001) [Pubmed]
  9. Amino acid neurotransmission and initiation of puberty: evidence from nonketotic hyperglycinemia in a female infant and gonadotropin-releasing hormone secretion by rat hypothalamic explants. Bourguignon, J.P., Jaeken, J., Gerard, A., de Zegher, F. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  10. beta-Carboline gamma-aminobutyric acidA receptor inverse agonists modulate gamma-aminobutyric acid via the loreclezole binding site as well as the benzodiazepine site. Stevenson, A., Wingrove, P.B., Whiting, P.J., Wafford, K.A. Mol. Pharmacol. (1995) [Pubmed]
  11. A behavioural and neurochemical study in rats of the pharmacology of loreclezole, a novel allosteric modulator of the GABAA receptor. Green, A.R., Misra, A., Murray, T.K., Snape, M.F., Cross, A.J. Neuropharmacology (1996) [Pubmed]
  12. Loreclezole inhibition of recombinant alpha1beta1gamma2L GABA(A) receptor single channel currents. Fisher, J.L., Hinkle, D.J., Macdonald, R.L. Neuropharmacology (2000) [Pubmed]
  13. Interactions between loreclezole, chlormethiazole and pentobarbitone at GABA(A) receptors: functional and binding studies. Zhong, Y., Simmonds, M.A. Br. J. Pharmacol. (1997) [Pubmed]
  14. Effects of the triazole derivative loreclezole (R72063) on stimulus induced ionic and field potential responses and on different patterns of epileptiform activity induced by low magnesium in rat entorhinal cortex-hippocampal slices. Zhang, C.L., Heinemann, U. Naunyn Schmiedebergs Arch. Pharmacol. (1992) [Pubmed]
  15. Single-dose efficacy evaluation of loreclezole in patients with photosensitive epilepsy. Overweg, J., De Beukelaar, F. Epilepsy Res. (1990) [Pubmed]
  16. Consequence of the presence of two different beta subunit isoforms in a GABA(A) receptor. Boulineau, N., Baur, R., Minier, F., Sigel, E. J. Neurochem. (2005) [Pubmed]
  17. Thymol, a constituent of thyme essential oil, is a positive allosteric modulator of human GABA(A) receptors and a homo-oligomeric GABA receptor from Drosophila melanogaster. Priestley, C.M., Williamson, E.M., Wafford, K.A., Sattelle, D.B. Br. J. Pharmacol. (2003) [Pubmed]
  18. Direct activation of GABAA receptors by loreclezole, an anticonvulsant drug with selectivity for the beta-subunit. Sanna, E., Murgia, A., Casula, A., Usala, M., Maciocco, E., Tuligi, G., Biggio, G. Neuropharmacology (1996) [Pubmed]
  19. Zurich Consensus Conference on New Antiepileptic Drugs. Introduction: goals. Wieser, H.G. Epilepsia (1994) [Pubmed]
  20. Compounds exhibiting selective efficacy for different beta subunits of human recombinant gamma-aminobutyric acid A receptors. Smith, A.J., Oxley, B., Malpas, S., Pillai, G.V., Simpson, P.B. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  21. Loreclezole enhances apparent desensitization of recombinant GABAA receptor currents. Donnelly, J.L., MacDonald, R.L. Neuropharmacology (1996) [Pubmed]
  22. U-89843A is a novel allosteric modulator of gamma-aminobutyric acidA receptors. Im, H.K., Im, W.B., Pregenzer, J.F., Carter, D.B., Hamilton, B.J. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  23. Efficacy and safety evaluation of loreclezole as add-on treatment in therapy-resistant epilepsy patients. Rentmeester, T., Hulsman, J. Epilepsy Res. (1991) [Pubmed]
  24. Loreclezole and La3+ differentiate cerebellar granule cell GABA(A) receptor subtypes. Mäkelä, R., Wisden, W., Korpi, E.R. Eur. J. Pharmacol. (1999) [Pubmed]
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