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
Način primene	Oralno
Pravni status
Pravni status	℞ (Prescription only);
Identifikatori
CAS broj	3613-73-8
ATC kod	none
PubChem	CID 197033
ChemSpider	170644
UNII	OD9237K1Z6
Hemijski podaci
Formula	C21H25N3
Molarna masa	319,443 g/mol

Latrepirdin (dimebolin, Dimebon) je antihistamin koji je u kliničkoj upotrebi u Rusiji od 1983.^[1]

U toku su istraživanja njegove potencijalne primene kao neuroprotektivnog leka u borbi protiv Alchajmerove bolesti, kao i mogućnosti nootropne upotrebe.^[2] Jedna od kliničkih studija u faze III za Alcheimerovu bolesti je utvrdila da on nije koristan. Tri druge studije su u toku.^[3] Kliničko ispitivanje za Hantingtonovu bolest nije bilo uspešno.^[4]

Farmakologija

Latrepirdin ima više mehanizama dejstva. On blokira dejstvo neurotoksičnih beta-amiloidnih proteina, inhibira L-tip kalcijumov kanal|kalcijumove kanale,^[5] modulara dejstvo AMPA i NMDA glutamatnih receptora,^[6] i može da ispolji neuroprotektivno dejstvo putem blokiranja bioloških meta koje učestvuju u permeabilnosti mitohondrijalnih pora,^[7] za koje se smatra da doprinose ćelijskom izumiranju vezanom za neurodegenerativne bolesti i proces starenja.^[8] On takođe blokira brojne druge receptore, uključujući α-adrenergičkai, 5-HT_2C, 5-HT_5A, i 5-HT₆.^[9] Latrepirdin nema antiholinergičko dejstvo.^[10]

Reference

^ Matveeva IA (1983). „Action of dimebon on histamine receptors”. Farmakologiia i Toksikologiia (на језику: руски). 46 (4): 27—29. PMID 6225678.
^ Shevtsova EF, Kireeva EG, Bachurin SO (2005). „Mitochondria as the target for neuroprotectors”. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (на језику: руски) (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 (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.
^ Grigorev VV, Dranyi OA, Bachurin SO (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.
^ Bachurin SO, Shevtsova EP, Kireeva EG, Oxenkrug GF, Sablin SO (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. ^{[мртва веза]}
^ „Medivation's Dimebon(TM) Maintains Statistically Significant Benefit on All Five Efficacy Endpoints in Alzheimer's Disease Trial After One Year of Therapy” (Саопштење). 11. 06. 2007.
^ 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.
^ 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 (на језику: руски). 56 (1): 22—4. PMID 8100727.

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Spoljašnje veze

[pmid6225678-1] Matveeva IA (1983). „Action of dimebon on histamine receptors”. Farmakologiia i Toksikologiia (на језику: руски). 46 (4): 27—29. PMID 6225678.

[pmid16250325-2] Shevtsova EF, Kireeva EG, Bachurin SO (2005). „Mitochondria as the target for neuroprotectors”. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (на језику: руски) (9): 13—17. PMID 16250325.

[medpagetoday-3] Novel Alzheimer's Drug Flops, MedPage Today, March 03, 2010

[HD-4] Phase III Failure Leads Medivation and Pfizer to Ditch Dimebon for Huntington Disease

[pmid11865327-5] Lermontova NN, Redkozubov AE, Shevtsova EF, Serkova TP, Kireeva EG, Bachurin SO (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.

[pmid14968164-6] Grigorev VV, Dranyi OA, Bachurin SO (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.

[pmid12853325-7] Bachurin SO, Shevtsova EP, Kireeva EG, Oxenkrug GF, Sablin SO (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. ^{[мртва веза]}

[8] „Medivation's Dimebon(TM) Maintains Statistically Significant Benefit on All Five Efficacy Endpoints in Alzheimer's Disease Trial After One Year of Therapy” (Саопштење). 11. 06. 2007.

[pmid18939977-9] 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.

[pmid8100727-10] 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 (на језику: руски). 56 (1): 22—4. PMID 8100727.

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