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Endozepine

Endozepines are endogenous compounds that bind to the benzodiazepine binding site on the GABAA receptor complex. That is to say, endozepines are the natural ligands of the benzodiazepine receptor. Endozepines may have sedative effects similar to benzodiazepine medications such as diazepam, or they may have opposite effects, depending on whether they are agonists, antagonists, or inverse agonists.

Endozepines have been linked to hepatic encephalopathy and have controversially been linked to some cases of recurrent stupor. Initially, the key diagnostic test is stupor which is sensitive to the benzodiazepine receptor antagonist flumazenil in the absences of exogenous benzodiazepines. Other roles include regulation of appetite and glucose metabolism, and processes relating to inflammation and pain signalling.

Potential candidates for these compounds are:

  • Oleamide
  • Nonpeptidic endozepines such as inosine
  • The protein diazepam binding inhibitor (DBI) and polypeptide fragments derived from it such as the octadecaneuropeptide ODN (DBI33-50) and triakontatetraneuropeptide (TTN)

References

References

  1. (Dec 2005). "Endozepines in recurrent stupor". Sleep Med Rev.
  2. Clavier T, Tonon MC, Foutel A. et al. Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study. ''Crit Care'' 2024; 18: 633. {{doi. 10.1186/s13054-014-0633-7
  3. Masmoudi-Kouki O, et al. Neuroprotection with the Endozepine Octadecaneuropeptide, ODN. ''Current Pharmaceutical Design'' 2018; 24(33): 3918-3925. {{doi. 10.2174/1381612824666181112111746
  4. Barbot M, et al. Glial Endozepines and Energy Balance: Old Peptides with New Tricks. ''Glia'' 2020; {{doi. 10.1002/glia.23927
  5. New NE, et al. Insulin evokes release of endozepines from astrocytes of the NTS to modulate glucose metabolism. ''bioRxiv'' 2024; {{doi. 10.1101/2024.05.03.592384
  6. Li X, Prudente AS, Prato V, Guo X, Hao H, Jones F, Figoli S, Mullen P, Wang Y, Tonello R, Lee SH, Shah S, Maffei B, Berta T, Du X, Gamper N. Peripheral gating of mechanosensation by glial diazepam binding inhibitor. ''J Clin Invest''. 2024 Jun 18;134(16):e176227. {{doi. 10.1172/JCI176227 {{PMID. 38888973
  7. Chen H, Moriceau S, Joseph A, Mailliet F, Li S, Tolle V, Duriez P, Dardennes R, Durand S, Carbonnier V, Stoll G, Sauvat A, Lachkar S, Aprahamian F, Alves Costa Silva C, Pan H, Montégut L, Anagnostopoulos G, Lambertucci F, Motiño O, Nogueira-Recalde U, Bourgin M, Mao M, Pan Y, Cerone A, Boedec E, Gouveia ZL, Marmorino F, Cremolini C, Derosa L, Zitvogel L, Kepp O, López-Otín C, Maiuri MC, Perez F, Gorwood P, Ramoz N, Oury F, Martins I, Kroemer G. Acyl-CoA binding protein for the experimental treatment of anorexia. ''Sci Transl Med''. 2024 Aug 14;16(760):eadl0715. {{doi. 10.1126/scitranslmed.adl0715 {{PMID. 39141698
  8. (2015). "Diversity and Functions of GABA Receptors: A Tribute to Hanns Möhler, Part A".
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neurotransmitters neuropeptides
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