Latrepirdin

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	197033
ChemSpider	170644
UNII	OD9237K1Z6
Hemijski podaci
Formula	C21H25N3
Mol. masa	319,443 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C21H25N3/c1-15-4-7-20-18(12-15)19-14-23(3)10-9-21(19)24(20)11-8-17-6-5-16(2)22-13-17/h4-7,12-13H,8-11,14H2,1-3H3 ; Key: JNODQFNWMXFMEV-UHFFFAOYSA-N
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

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-HT_2C, 5-HT_5A, i 5-HT₆.^[12] Latrepirdin nema antiholinergičko dejstvo.^[13]

Reference uredi

↑ 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. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ 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.
↑ 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. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Matveeva IA (July 1983). „Action of dimebon on histamine receptors” (Russian). Farmakologiia i Toksikologiia 46 (4): 27–29. PMID 6225678.
↑ Shevtsova EF, Kireeva EG, Bachurin SO (2005). „Mitochondria as the target for neuroprotectors” (Russian). Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (9): 13–17. PMID 16250325.
↑ Novel Alzheimer's Drug Flops, MedPage Today, March 03, 2010
↑ Phase III Failure Leads Medivation and Pfizer to Ditch Dimebon for Huntington Disease
↑ 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. DOI:10.1023/A:1017972709652. PMID 11865327.
↑ 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. DOI:10.1023/B:BEBM.0000017097.75818.14. PMID 14968164.
↑ 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. DOI:10.1111/j.1749-6632.2003.tb07541.x. PMID 12853325. ^{[mrtav link]}
↑ "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.
↑ Wu J, Li Q, Bezprozvanny I (2008). „Evaluation of Dimebon in cellular model of Huntington's disease”. Molecular Neurodegeneration 3: 15. DOI:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.
↑ 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]” (Russian). Eksperimental'naia I Klinicheskaia Farmakologiia 56 (1): 22–4. PMID 8100727.

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[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. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. 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. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[pmid6225678-4] Matveeva IA (July 1983). „Action of dimebon on histamine receptors” (Russian). Farmakologiia i Toksikologiia 46 (4): 27–29. PMID 6225678.

[pmid16250325-5] Shevtsova EF, Kireeva EG, Bachurin SO (2005). „Mitochondria as the target for neuroprotectors” (Russian). Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (9): 13–17. PMID 16250325.

[medpagetoday-6] Novel Alzheimer's Drug Flops, MedPage Today, March 03, 2010

[HD-7] Phase III Failure Leads Medivation and Pfizer to Ditch Dimebon for Huntington Disease

[pmid11865327-8] 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. DOI:10.1023/A:1017972709652. PMID 11865327.

[pmid14968164-9] 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. DOI:10.1023/B:BEBM.0000017097.75818.14. PMID 14968164.

[pmid12853325-10] 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. DOI:10.1111/j.1749-6632.2003.tb07541.x. PMID 12853325. ^{[mrtav link]}

[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.

[pmid18939977-12] Wu J, Li Q, Bezprozvanny I (2008). „Evaluation of Dimebon in cellular model of Huntington's disease”. Molecular Neurodegeneration 3: 15. DOI:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.

[pmid8100727-13] 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]” (Russian). Eksperimental'naia I Klinicheskaia Farmakologiia 56 (1): 22–4. PMID 8100727.

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