Dihidreksidin

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Dihidreksidin
(IUPAC) ime
5,6,6a,7,8,12b-heksahidro-benzo(a)fenantridin-10,11-diol
Klinički podaci
Identifikatori
CAS broj 137417-08-4
ATC kod nije dodeljen
PubChem[1][2] 5311070
UNII 32D64VH037 DaY
ChEMBL[3] CHEMBL25856 DaY
Hemijski podaci
Formula C17H17NO2 
Mol. masa 267,322 g/mol
SMILES eMolekuli & PubHem
Farmakoinformacioni podaci
Trudnoća ?
Pravni status

Dihidreksidin (DAR-0100) je umereno selektivni puni agonist dopaminskih D1 i D5 receptora.[4] On je oko 10 puta selektivniji za D1 i D5 nego za D2 receptor.[5] Mada dihidreksidin ima delimičan afinitet za D2 receptor, on ima funkcionalno selektivanu D2 signalizaciju, iz kog razloga se ne ponaša kao D2 agonist.[6]

Dihidreksidin je pokazao impresivno antiparkinsonsko dejstvo u modelu na primatima,[7] i bio je ispitivan za tretman Parkinsonove bolesti.[8] U ranim kliničkim ispitivanjima lek je korišćen intravenozno što je dovelo do znatene hipotenzije tako da je razvoj zaustavljen.[9] Razvoj je obnovljen kad je pokazano da su manje supkutane doze bezbedne.[10] Tome je sledila pilot studija za šizofreniju[11] i klinička ispitivanja s ciljem procenjivanja njegove efikasnosti u poboljšanju kognitivnog i memorijskog deficita kod šizofrenije i šizotipnog poremećaja.

Objavleno je više pregleda relevantnositi ovog jedinjenja.[12][13][14]

Reference[uredi | uredi kod]

  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. ↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594.  edit
  4. ↑ Lovenberg TW, Brewster WK, Mottola DM, Lee RC, Riggs RM, Nichols DE, Lewis MH, Mailman RB. (1989). „Dihydrexidine, a novel selective high potency full dopamine D-1 receptor agonist.”. Eur J Pharmacol. 166 (1): 111–113. PMID 2572425. 
  5. ↑ Mottola DM, Brewster WK, Cook LL, Nichols DE, Mailman RB. (1992). „Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist.”. J Pharmacol Exp Ther. 262 (1): 383–393. PMID 1352553. 
  6. ↑ Darney KJ Jr, Lewis MH, Brewster WK, Nichols DE, Mailman RB. (1991). „Behavioral effects in the rat of dihydrexidine, a high-potency, full-efficacy D1 dopamine receptor agonist.”. Neuropsychopharmacology. 5 (3): 187–195. PMID 1684499. 
  7. ↑ Taylor JR, Lawrence MS, Redmond DE Jr, Elsworth JD, Roth RH, Nichols DE, Mailman RB. (1991). „Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys.”. Eur J Pharmacol. 199 (3): 389–391. PMID 1680717. 
  8. ↑ Mailman RB, Nichols DE. (1998). „Dopamine D1 receptor agonists as antiparkinson drugs.”. Trends Pharmacol Sci. 19 (7): 255–256. PMID 9703756. 
  9. ↑ Blanchet PJ, Fang J, Gillespie M, Sabounjian L, Locke KW, Gammans R, Mouradian MM, Chase TN. (1998). „Effects of the full dopamine D1 receptor agonist dihydrexidine in Parkinson's disease.”. Clin Neuropharmacol. 21 (6): 339–343. PMID 9844789. 
  10. ↑ George MS, Molnar CE, Grenesko EL, Anderson B, Mu Q, Johnson K, Nahas Z, Knable M, Fernandes P, Juncos J, Huang X, Nichols DE, Mailman RB. (2007). „A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia.”. Schizophr Res. 93 (1-3): 42–50. PMID 17467956. 
  11. ↑ Mu Q, Johnson K, Morgan PS, Grenesko EL, Molnar CE, Anderson B, Nahas Z, Kozel FA, Kose S, Knable M, Fernandes P, Nichols DE, Mailman RB, George MS. (2007). „A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia.”. Schizophr Res. 94 (1-3): 332–341. PMID 17596915. 
  12. ↑ Mailman R, Huang X, Nichols DE. (2001). „Parkinson's disease and D1 dopamine receptors.”. Curr Opin Investig Drugs. 2 (11): 1582–1591. PMID 11763161. 
  13. ↑ Salmi P, Isacson R, Kull B. (2004). „Dihydrexidine--the first full dopamine D1 receptor agonist.”. CNS Drug Rev. 10 (3): 230–242. PMID 15492773. 
  14. ↑ Zhang J, Xiong B, Zhen X, Zhang A. (2009). „Dopamine D1 receptor ligands: where are we now and where are we going.”. Med Res Rev. 29 (2): 272–294. DOI:10.1002/med.20130. PMID 18642350. 

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