Antagonist H3 receptora
Antagonist H3 receptora je klasifikacija lekova koji se koriste za blokiranje dejstva histamina na H3 receptoru. Za razliku od H1 i H2 receptora koji prvenstveno imaju periferno dejstvo, ali uzrokuju sedaciju ako se blokiraju u mozgu, H3 receptori se prvenstveno nalaze u mozgu i inhibiraju autoreceptore locirane na histaminergičnim nervnim terminalima, čime modulišu otpuštanje histamina. Histaminsko otpuštanje u mozgu inicira sekundarno otpuštanje ekscitatornih neurotransmitera puput glutamata i acetilholina stimulacijom H1 receptora u moždanoj kori. Konsekventno za razliku od H1 antagonista koji proizvode sedaciju, H3 antagonisti imaju stimulantne i nootropne efekte, i istražuju se kao potencijalni lekovi u tretmanu neurodegenerativnih oboljenja kao što je Alchajmerova bolest.
Primeri selektivnih H3 antagonista su klobenpropit,[1] ABT-239,[2] ciproksifan,[3], konesin, i A-349,821.[4]
- ↑ Yoneyama H, Shimoda A, Araki L, et al. (March 2008). „Efficient approaches to S-alkyl-N-alkylisothioureas: syntheses of histamine H3 antagonist clobenpropit and its analogues”. J. Org. Chem. 73 (6): 2096–104. DOI:10.1021/jo702181x. PMID 18278935.
- ↑ Fox GB, Esbenshade TA, Pan JB, Radek RJ, Krueger KM, Yao BB, Browman KE, Buckley MJ, Ballard ME, Komater VA, Miner H, Zhang M, Faghih R, Rueter LE, Bitner RS, Drescher KU, Wetter J, Marsh K, Lemaire M, Porsolt RD, Bennani YL, Sullivan JP, Cowart MD, Decker MW, Hancock AA (2005). „Pharmacological properties of ABT-239 [4-(22-[(2R)-2-Methylpyrrolidinyl]ethylbenzofuran-5-yl)benzonitrile]: II. Neurophysiological characterization and broad preclinical efficacy in cognition and schizophrenia of a potent and selective histamine H3 receptor antagonist”. J. Pharmacol. Exp. Ther. 313 (1): 176–90. DOI:10.1124/jpet.104.078402. PMID 15608077.
- ↑ LLigneau X, Lin J, Vanni-Mercier G, Jouvet M, Muir JL, Ganellin CR, Stark H, Elz S, Schunack W, Schwartz J (November 1998). „Neurochemical and behavioral effects of ciproxifan, a potent histamine H3-receptor antagonist”. J. Pharmacol. Exp. Ther. 287 (2): 658–66. PMID 9808693.
- ↑ Esbenshade TA, Fox GB, Krueger KM, Baranowski JL, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan JB, Faghih R, Bennani YL, Williams M, Hancock AA (2004-01-09). „Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist”. Biochemical Pharmacology 68 (5): 933–45. DOI:10.1016/j.bcp.2004.05.048. PMID 15294456.