Loreclezole

Loreclezole
Clinical data
ATC code none
Identifiers
CAS Number 117857-45-1 YesY
PubChem (CID) 3034012
IUPHAR/BPS 5466
ChemSpider 2298566 YesY
UNII 6DJ32STZ5W YesY
KEGG D04780 YesY
Chemical and physical data
Formula C10H6Cl3N3
Molar mass 274.534 g/mol
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Loreclezole is a sedative and an anticonvulsant which acts as a GABAA receptor positive allosteric modulator.[1] The binding site of loreclezole has been shown experimentally to be shared by valerenic acid, an extract of the root of the valerian plant.[2] Structurally, loreclezole is a triazole derivative. In animal seizure models, loreclezole is protective against pentylenetetrazol seizures but is less active in the maximal electroshock test.[3] In addition, at low, nontoxic doses, the drug has anti-absence activity in a genetic model of generalized absence epilepsy. Consequently, loreclezole has a profile of activity similar to that of benzodiazepines. A potential benzodiazepine-like interaction with GABA receptors is suggested by the observation that the anticonvulsant effects of loreclezole can be reversed by benzodiazepine receptor inverse agonists. The benzodiazepine antagonist flumazenil, however, fails to alter the anticonvulsant activity of loreclezole, indicating that loreclezole is not a benzodiazepine receptor agonist. Using native rat and cloned human GABA-A receptors, loreclezole strongly potentiated GABA-activated chloride current. However, activity of the drug did not require the presence of the γ-subunit and was not blocked by flumazenil, confirming that loreclezole does not interact with the benzodiazepine recognition site.

References

  1. ↑ Wingrove, P. B.; Wafford, K. A.; Bain, C.; Whiting, P. J. (1994). "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". Proceedings of the National Academy of Sciences of the United States of America. 91 (10): 4569–4573. doi:10.1073/pnas.91.10.4569. PMC 43827Freely accessible. PMID 8183949.
  2. ↑ Khom, S.; Baburin, I.; Timin, E.; Hohaus, A.; Trauner, G.; Kopp, B.; Hering, S. (2007). "Valerenic acid potentiates and inhibits GABAA receptors: Molecular mechanism and subunit specificity". Neuropharmacology. 53 (1): 178–187. doi:10.1016/j.neuropharm.2007.04.018. PMID 17585957.
  3. ↑ Rogawski, M (1996). "Epilepsy". In Pullan, L; Patel, J. Neurotherapeutics: Emerging Strategies. Humana Press. pp. 193–273.


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