BW373U86

BW373U86
(IUPAC) ime
4-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide
Klinički podaci
Identifikatori
CAS broj 150428-54-9
ATC kod ?
PubChem[1][2] 119029
Hemijski podaci
Formula C27H37N3O2 
Mol. masa 435.602 g/mol
SMILES eMolekuli & PubHem
Sinonimi (+)BW373U86
Farmakoinformacioni podaci
Trudnoća ?
Pravni status

(+)BW373U86 je opioidni analgetik koji se koristi u naučnim istraživanjma.[3][4]

BW373U86 je selektivni agonist δ-opioidnog receptora, sa aproksimativno 15x većim afinitetom za δ-opioidni nego za μ-opioidni receptor.[5] On se pokazao kao potentan analgetik[6] i antidepresant u životinjskim studijama,[7] koji inicira oslobađanje neuronskog faktora rasta BDNF,[8][9] ali je njegova upotrebljivost ograničena usled stvaranja konvulzija na visokim dozama,[10][11] mada su ti efekti umanjeni kad se dozira zajedno sa μ-opioidnim agonistima.[12] Još jedna prednost kombinovanja je da BW373U86 poništava respiratornu depresiju proizvedenu μ-opioidnim agonistima, bez vršenja uticaja na umanjenje bola.[13]

Jedno dodatno svojstvo BW373U86 je da zaštićuje ćelije mišića srca u ishemijskim uslovima (kiseonična deprivacija, kao što je to slučaj kod srčanog udara). Mehanizam za to je kompleksan i možda nije vezan sa delta agonistnim efektima.[14][15][16]

Literatura

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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. ↑ Calderon SN, Rice KC, Rothman RB, Porreca F, Flippen-Anderson JL, Kayakiri H, Xu H, Becketts K, Smith LE, Bilsky EJ, Davis P, Horvath R (1997). „Probes for narcotic receptor mediated phenomena. 23. Synthesis, opioid receptor binding, and bioassay of the highly selective delta agonist (+)-4-[(alpha R)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N,N-diethylbenzamide (SNC 80) and related novel nonpeptide delta opioid receptor ligands”. J. Med. Chem. 40 (5): 695–704. DOI:10.1021/jm960319n. PMID 9057856. 
  4. ↑ Thomas JB, Herault XM, Rothman RB, Atkinson RN, Burgess JP, Mascarella SW, Dersch CM, Xu H i dr.. (March 2001). „Factors influencing agonist potency and selectivity for the opioid delta receptor are revealed in structure-activity relationship studies of the 4-(N-substituted-4-piperidinyl)arylamino-N,N-diethylbenzamides.”. Journal of medicinal chemistry 44 (6): 972–87. PMID 11300879. 
  5. ↑ Chang KJ, Rigdon GC, Howard JL, McNutt RW (November 1993). „A novel, potent and selective nonpeptidic delta opioid receptor agonist BW373U86”. The Journal of pharmacology and experimental therapeutics 267 (2): 852–7. PMID 8246159. 
  6. ↑ Broom D. C., Nitsche JF, Pintar JE, Rice KC, Woods JH, Traynor JR (November 2002). „Comparison of Receptor Mechanisms and Efficacy Requirements for delta -Agonist-Induced Convulsive Activity and Antinociception in Mice”. Journal of Pharmacology and Experimental Therapeutics 303 (2): 723–729. DOI:10.1124/jpet.102.036525. PMID 12388657. 
  7. ↑ Broom D, Jutkiewicz EM, Folk JE, Traynor JR, Rice KC, Woods JH (June 2002). „Nonpeptidic δ-opioid Receptor Agonists Reduce Immobility in the Forced Swim Assay in Rats”. Neuropsychopharmacology 26 (6): 744–755. DOI:10.1016/S0893-133X(01)00413-4. PMID 12007745. 
  8. ↑ Torregrossa Mary M., Folk John E., Rice Kenner C., Watson Stanley J., Woods James H. (November 2005). „Chronic administration of the delta opioid receptor agonist (+)BW373U86 and antidepressants on behavior in the forced swim test and BDNF mRNA expression in rats”. Psychopharmacology 183 (1): 31–40. DOI:10.1007/s00213-005-0113-5. PMC 1315298. PMID 16220339. 
  9. ↑ Torregrossa Mary M, Isgor Ceylan, Folk John E, Rice Kenner C, Watson Stanley J, Woods James H (April 2004). „The δ-Opioid Receptor Agonist (+)BW373U86 Regulates BDNF mRNA Expression in Rats”. Neuropsychopharmacology 29 (4): 649–659. DOI:10.1038/sj.npp.1300345. PMID 14647482. 
  10. ↑ Comer SD, Hoenicke EM, Sable AI, McNutt RW, Chang KJ, De Costa BR, Mosberg HI, Woods JH (November 1993). „Convulsive effects of systemic administration of the delta opioid agonist BW373U86 in mice”. The Journal of pharmacology and experimental therapeutics 267 (2): 888–95. PMID 8246164. 
  11. ↑ Broom Daniel, Jutkiewicz Emily, Folk John, Traynor John, Rice Kenner, Woods James (October 2002). „Convulsant activity of a non-peptidic δ-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats”. Psychopharmacology 164 (1): 42–48. DOI:10.1007/s00213-002-1179-y. PMID 12373418. 
  12. ↑ O'Neill SJ, Collins MA, Pettit HO, McNutt RW, Chang KJ (July 1997). „Antagonistic modulation between the delta opioid agonist BW373U86 and the mu opioid agonist fentanyl in mice”. The Journal of pharmacology and experimental therapeutics 282 (1): 271–7. PMID 9223564. 
  13. ↑ Su YF, McNutt RW, Chang KJ (December 1998). „Delta-opioid ligands reverse alfentanil-induced respiratory depression but not antinociception”. The Journal of pharmacology and experimental therapeutics 287 (3): 815–23. PMID 9864259. 
  14. ↑ Patel H, Hsu A, Moore J, Gross GJ (August 2001). „BW373U86, a δ Opioid Agonist, Partially Mediates Delayed Cardioprotection via a Free Radical Mechanism that is Independent of Opioid Receptor Stimulation”. Journal of Molecular and Cellular Cardiology 33 (8): 1455–1465. DOI:10.1006/jmcc.2001.1408. PMID 11448134. 
  15. ↑ Patel H, Hsu AK, Gross GJ (May 2004). „COX-2 and iNOS in opioid-induced delayed cardioprotection in the intact rat”. Life Sciences 75 (2): 129–140. DOI:10.1016/j.lfs.2003.10.036. PMID 15120566. 
  16. ↑ Gross E. R., Hsu A. K., Gross G. J. (July 2007). „GSK3β inhibition and KATP channel opening mediate acute opioid-induced cardioprotection at reperfusion”. Basic Research in Cardiology 102 (4): 341–349. DOI:10.1007/s00395-007-0651-6. PMID 17450314. 

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