Récepteurs associés aux amines traces

Les récepteurs associés aux amines traces (TAAR), parfois appelés récepteurs aux amines traces (TA ou TAR), sont une classe de récepteurs couplés aux protéines G découverts en 2001[1],[2]. TAAR1, le premier des six TAAR humains, est un récepteur endogène pour les traces d'amines phénéthylamine, tyramine et tryptamine. – dérivés métaboliques des acides aminés phénylalanine, tyrosine et tryptophane, respectivement – l’éphédrine, ainsi que les psychostimulants synthétiques amphétamine, méthamphétamine et MDMA[3],[4],[5],[6],[7],[8]. TAAR1 des mammifères est également un récepteur pour les thyronamines, des parents décarboxylés et désiodés des hormones thyroïdiennes[5]. Les récepteurs TAAR2–TAAR9 fonctionnent comme des récepteurs olfactifs pour les odorants aminés volatils chez les vertébrés[9].

L'Ulotaront fut un agoniste TAAR1 en phase 3 d'essais cliniques pour la schizophrénie et des essais antérieurs pour la psychose de la maladie de Parkinson. Le médicament a obtenu le label « Breakthrough » de la FDA américaine[10],[11],[12].

Références

  1. ↑ « Trace amines: identification of a family of mammalian G protein-coupled receptors », Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no 16,‎ , p. 8966–8971 (PMID 11459929, PMCID 55357, DOI 10.1073/pnas.151105198)
  2. ↑ « Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor », Molecular Pharmacology, vol. 60, no 6,‎ , p. 1181–1188 (PMID 11723224, DOI 10.1124/mol.60.6.1181)
  3. ↑ « The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity », Journal of Neurochemistry, vol. 116, no 2,‎ , p. 164–176 (PMID 21073468, PMCID 3005101, DOI 10.1111/j.1471-4159.2010.07109.x)
  4. ↑ « In-vivo pharmacology of Trace-Amine Associated Receptor 1 », European Journal of Pharmacology, vol. 763, no Pt B,‎ , p. 136–142 (PMID 26093041, DOI 10.1016/j.ejphar.2015.06.026)
  5. ↑ a et b « 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone », Nature Medicine, vol. 10, no 6,‎ , p. 638–642 (PMID 15146179, DOI 10.1038/nm1051, S2CID 2389946)
  6. ↑ « A renaissance in trace amines inspired by a novel GPCR family », Trends in Pharmacological Sciences, vol. 26, no 5,‎ , p. 274–281 (PMID 15860375, DOI 10.1016/j.tips.2005.03.007)
  7. ↑ « Trace amine-associated receptor agonists: synthesis and evaluation of thyronamines and related analogues », Journal of Medicinal Chemistry, vol. 49, no 3,‎ , p. 1101–1112 (PMID 16451074, DOI 10.1021/jm0505718)
  8. ↑ « Trace amine-associated receptor 1-Family archetype or iconoclast? », Pharmacology & Therapeutics, vol. 116, no 3,‎ , p. 355–390 (PMID 17888514, PMCID 2767338, DOI 10.1016/j.pharmthera.2007.06.007)
  9. ↑ « Trace amine-associated receptors: ligands, neural circuits, and behaviors », Current Opinion in Neurobiology, vol. 34,‎ , p. 1–7 (PMID 25616211, PMCID 4508243, DOI 10.1016/j.conb.2015.01.001) :

    « Roles for another receptor are supported by TAAR5-independent trimethylamine anosmias in humans [32]. ... Several TAARs detect volatile and aversive amines, but the olfactory system is capable of discarding ligand-based or function-based constraints on TAAR evolution. Particular TAARs have mutated to recognize new ligands, with almost an entire teleost clade losing the canonical amine-recognition motif. Furthermore, while some TAARs detect aversive odors, TAAR-mediated behaviors can vary across species. ... The ability of particular TAARs to mediate aversion and attraction behavior provides an exciting opportunity for mechanistic unraveling of odor valence encoding. »



    Figure 2: Table of ligands, expression patterns, and species-specific behavioral responses for each TAAR
  10. ↑ « Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia », ACS Medicinal Chemistry Letters, vol. 13, no 1,‎ , p. 92–98 (PMID 35047111, PMCID 8762745, DOI 10.1021/acsmedchemlett.1c00527)
  11. ↑ « Sunovion: creating therapies to help transform people's lives », www.sunovion.com (consulté le )
  12. ↑ (en-US) « Sunovion and PsychoGenics Announce that SEP-363856 Has Received FDA Breakthrough Therapy Designation for the Treatment of People with Schizophrenia », news.sunovion.com (consulté le )

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