BW373U86

drugbox
IUPAC_name = 4- [(R)- [(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl] -(3-hydroxyphenyl)methyl] -N,N-diethylbenzamide

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CAS_number = 150428-54-9
synonyms = (+)BW373U86
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PubChem = 119029
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C = 27 | H = 37 | N = 3 | O = 2
molecular_weight = 435.602 g/mol
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(+)BW373U86 is an opioid analgesic drug used in scientific research.cite journal | author = 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 | title = 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 | journal = J. Med. Chem. | volume = 40 | issue = 5 | pages = 695–704 | year = 1997 | pmid = 9057856 | doi = 10.1021/jm960319n | issn = ] [Thomas JB, Herault XM, Rothman RB, Atkinson RN, Burgess JP, Mascarella SW, Dersch CM, Xu H, Flippen-Anderson JL, George CF, Carroll FI. 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". 2001 Mar 15;44(6):972-87. PMID 11300879]

BW373U86 is a selective agonist for the δ-opioid receptor, with approximately 15x stronger affinity for the δ-opioid than the μ-opioid receptor. [Chang KJ, Rigdon GC, Howard JL, McNutt RW. A novel, potent and selective nonpeptidic delta opioid receptor agonist BW373U86. "Journal of Pharmacology and Experimental Therapeutics". 1993 Nov;267(2):852-7. PMID 8246159] It has potent analgesic [Broom DC, Nitsche JF, Pintar JE, Rice KC, Woods JH, Traynor JR. Comparison of receptor mechanisms and efficacy requirements for delta-agonist-induced convulsive activity and antinociception in mice. "Journal of Pharmacology and Experimental Therapeutics". 2002 Nov;303(2):723-9. PMID 12388657] and antidepressant effects in animal studies, [Broom DC, Jutkiewicz EM, Folk JE, Traynor JR, Rice KC, Woods JH. Nonpeptidic delta-opioid receptor agonists reduce immobility in the forced swim assay in rats. "Neuropsychopharmacology". 2002 Jun;26(6):744-55. PMID 12007745] and triggers release of the neural growth factor BDNF, [Torregrossa MM, Folk JE, Rice KC, Watson SJ, Woods JH. 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 (Berlin)". 2005 Nov;183(1):31-40. PMID 16220339] [Torregrossa MM, Isgor C, Folk JE, Rice KC, Watson SJ, Woods JH. The delta-opioid receptor agonist (+)BW373U86 regulates BDNF mRNA expression in rats. "Neuropsychopharmacology". 2004 Apr;29(4):649-59. PMID 14647482] but its usefulness is limited by producing convulsions at high doses, [Comer SD, Hoenicke EM, Sable AI, McNutt RW, Chang KJ, De Costa BR, Mosberg HI, Woods JH. Convulsive effects of systemic administration of the delta opioid agonist BW373U86 in mice. "Journal of Pharmacology and Experimental Therapeutics". 1993 Nov;267(2):888-95. PMID 8246164] [Broom DC, Jutkiewicz EM, Folk JE, Traynor JR, Rice KC, Woods JH. Convulsant activity of a non-peptidic delta-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats. "Psychopharmacology (Berlin)". 2002 Oct;164(1):42-8. PMID 12373418] although the convulsive effect is reduced when it is co-administered with μ-opioid agonists. [O'Neill SJ, Collins MA, Pettit HO, McNutt RW, Chang KJ. Antagonistic modulation between the delta opioid agonist BW373U86 and the mu opioid agonist fentanyl in mice. "Journal of Pharmacology and Experimental Therapeutics". 1997 Jul;282(1):271-7. PMID 9223564] Another advantage of the combination is that BW373U86 reverses the respiratory depression produced by μ-opioid agonists, without affecting pain relief. [Su YF, McNutt RW, Chang KJ. Delta-opioid ligands reverse alfentanil-induced respiratory depression but not antinociception. "Journal of Pharmacology and Experimental Therapeutics". 1998 Dec;287(3):815-23. PMID 9864259]

Another useful effect of BW373U86 is that it protects heart muscle cells from death in conditions of ischemia (oxygen deprivation, such as in heart attack). The mechanism for this is complex and may be separate from its delta agonist effects. [Patel HH, Hsu A, Moore J, Gross GJ. BW373U86, a delta opioid agonist, partially mediates delayed cardioprotection via a free radical mechanism that is independent of opioid receptor stimulation. "Journal of Molecular and Cellular Cardiology". 2001 Aug;33(8):1455-65. PMID 11448134] [Patel HH, Hsu AK, Gross GJ. COX-2 and iNOS in opioid-induced delayed cardioprotection in the intact rat. "Life Sciences". 2004 May 28;75(2):129-40. PMID 15120566] [Gross ER, Hsu AK, Gross GJ. GSK3beta inhibition and K(ATP) channel opening mediate acute opioid-induced cardioprotection at reperfusion. "Basic Research in Cardiology". 2007 Jul;102(4):341-9. PMID 17450314]

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