Latrepirdin

Iz Wikipedije, slobodne enciklopedije
Latrepirdin
(IUPAC) ime
2,3,4,5-tetrahidro-2,8-dimetil-5-(2-(6-metil-3-piridil)etil)-1H-pirido(4,3-b)indol
Klinički podaci
Identifikatori
CAS broj 3613-73-8
ATC kod nije dodeljen
PubChem[1][2] 197033
ChemSpider[3] 170644
UNII OD9237K1Z6 YesY
Hemijski podaci
Formula C21H25N3 
Mol. masa 319,443 g/mol
SMILES eMolekuli & PubHem
Farmakoinformacioni podaci
Trudnoća  ?
Pravni status Prescription only
Način primene Oralno

Latrepirdin (dimebolin, Dimebon) je antihistamin koji je u kliničkoj upotrebi u Rusiji od 1983.[4]

U toku su istraživanja njegove potencijalne primene kao neuroprotektivnog leka u borbi protiv Alchajmerove bolesti, kao i mogućnosti nootropne upotrebe.[5] Jedna od kliničkih studija u faze III za Alcheimerovu bolesti je utvrdila da on nije koristan. Tri druge studije su u toku.[6] Kliničko ispitivanje za Hantingtonovu bolest nije bilo uspešno.[7]

Farmakologija[uredi - уреди | uredi izvor]

Latrepirdin ima više mehanizama dejstva. On blokira dejstvo neurotoksičnih beta-amiloidnih proteina, inhibira L-tip kalcijumov kanal|kalcijumove kanale,[8] modulara dejstvo AMPA i NMDA glutamatnih receptora,[9] i može da ispolji neuroprotektivno dejstvo putem blokiranja bioloških meta koje učestvuju u permeabilnosti mitohondrijalnih pora,[10] za koje se smatra da doprinose ćelijskom izumiranju vezanom za neurodegenerativne bolesti i proces starenja.[11] On takođe blokira brojne druge receptore, uključujući α-adrenergičkai, 5-HT2C, 5-HT5A, i 5-HT6.[12] Latrepirdin nema antiholinergičko dejstvo.[13]

Reference[uredi - уреди | uredi izvor]

  1. Li Q, Cheng T, Wang Y, Bryant SH (2010). "PubChem as a public resource for drug discovery.". Drug Discov Today 15 (23-24): 1052–7. PMID 20970519. doi:10.1016/j.drudis.2010.10.003.  edit
  2. Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). "Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities". Annual Reports in Computational Chemistry 4: 217–241. doi:10.1016/S1574-1400(08)00012-1. 
  3. Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). "Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining". J Cheminform 2 (1): 3. PMID 20331846. doi:10.1186/1758-2946-2-3.  edit
  4. Matveeva IA (July 1983). "Action of dimebon on histamine receptors". Farmakologiia i Toksikologiia (in Russian) 46 (4): 27–29. PMID 6225678. 
  5. Shevtsova EF, Kireeva EG, Bachurin SO (2005). "Mitochondria as the target for neuroprotectors". Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (in Russian) (9): 13–17. PMID 16250325. 
  6. Novel Alzheimer's Drug Flops, MedPage Today, March 03, 2010
  7. Phase III Failure Leads Medivation and Pfizer to Ditch Dimebon for Huntington Disease
  8. Lermontova NN, Redkozubov AE, Shevtsova EF, Serkova TP, Kireeva EG, Bachurin SO (November 2001). "Dimebon and tacrine inhibit neurotoxic action of beta-amyloid in culture and block L-type Ca(2+) channels". Bulletin of Experimental Biology and Medicine 132 (5): 1079–1083. PMID 11865327. doi:10.1023/A:1017972709652. 
  9. Grigorev VV, Dranyi OA, Bachurin SO (November 2003). "Comparative study of action mechanisms of dimebon and memantine on AMPA- and NMDA-subtypes glutamate receptors in rat cerebral neurons". Bull Exp Biol Med 136 (5): 474–477. PMID 14968164. doi:10.1023/B:BEBM.0000017097.75818.14. 
  10. Bachurin SO, Shevtsova EP, Kireeva EG, Oxenkrug GF, Sablin SO (May 2003). "Mitochondria as a target for neurotoxins and neuroprotective agents". Annals of the New York Academy of Sciences 993: 334–44; discussion 345–9. PMID 12853325. doi:10.1111/j.1749-6632.2003.tb07541.x. 
  11. "Medivation's Dimebon(TM) Maintains Statistically Significant Benefit on All Five Efficacy Endpoints in Alzheimer's Disease Trial After One Year of Therapy" (Press release). 2007-06-11. 
  12. Wu J, Li Q, Bezprozvanny I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease". Molecular Neurodegeneration 3: 15. PMC 2577671. PMID 18939977. doi:10.1186/1750-1326-3-15. 
  13. Gankina EM, Porodenko NV, Kondratenko TI, Severin ES, Kaminka ME, Mashkovskiĭ MD (1993). "[The effect of antihistaminic preparations on the binding of labelled mepyramine, ketanserin and quinuclidinyl benzilate in the rat brain]". Eksperimental'naia I Klinicheskaia Farmakologiia (in Russian) 56 (1): 22–4. PMID 8100727. 

Vidi još[uredi - уреди | uredi izvor]

Spoljašnje veze[uredi - уреди | uredi izvor]