Abstract
Since a μ-opioid receptor gene containing multiple exons has been identified, the variety of splice variants for μ-opioid receptors have been reported in various species. Amidino-TAPA and IBNtxA have been discovered as new analgesics with different pharmacological profiles from morphine. These new analgesics show a very potent analgesic effect but do not have dependence liability. Interestingly, these analgesics show the selectivity to the morphine-insensitive μ-opioid receptor splice variants. The splice variants, sensitive to these new analgesics but insensitive to morphine, may be a better molecular target to develop the analgesics without side effects.
Keywords: μ-Opioid receptor, Splice variant, Narcotic analgesics, Amidino-TAPA, IBNtxA, Molecular target.
[PMID: 6323950]
[http://dx.doi.org/10.1016/0024-3205(86)90217-1] [PMID: 2872563]
[http://dx.doi.org/10.1073/pnas.78.10.6181] [PMID: 6273857]
[http://dx.doi.org/10.1097/00002826-199302000-00001] [PMID: 8093680]
[http://dx.doi.org/10.1016/0922-4106(94)90072-8] [PMID: 7805771]
[http://dx.doi.org/10.1016/S0014-2999(99)00181-8] [PMID: 10374711]
[http://dx.doi.org/10.1016/S0014-2999(99)00065-5] [PMID: 10206177]
[http://dx.doi.org/10.1016/0006-8993(85)91226-0] [PMID: 3000528]
[http://dx.doi.org/10.1016/0006-8993(85)91227-2] [PMID: 3000529]
[http://dx.doi.org/10.1016/0006-8993(85)91273-9] [PMID: 4084809]
[http://dx.doi.org/10.1126/science.1335167] [PMID: 1335167]
[http://dx.doi.org/10.1073/pnas.89.24.12048] [PMID: 1334555]
[PMID: 8393525]
[http://dx.doi.org/10.1016/0014-5793(93)81011-N] [PMID: 8394245]
[http://dx.doi.org/10.1073/pnas.90.21.10230] [PMID: 8234282]
[http://dx.doi.org/10.1016/0014-5793(94)01129-X] [PMID: 7957926]
[http://dx.doi.org/10.1016/0014-5793(95)00028-8] [PMID: 7532594]
[http://dx.doi.org/10.1016/j.gene.2006.10.017] [PMID: 17156941]
[http://dx.doi.org/10.1016/j.gene.2007.02.004] [PMID: 17398041]
[http://dx.doi.org/10.1007/s00109-003-0514-z] [PMID: 14991152]
[http://dx.doi.org/10.1124/mol.56.2.396] [PMID: 10419560]
[http://dx.doi.org/10.1016/S0014-5793(00)01095-4] [PMID: 10682855]
[http://dx.doi.org/10.1073/pnas.241296098] [PMID: 11717463]
[http://dx.doi.org/10.1124/mol.105.011858] [PMID: 15939800]
[http://dx.doi.org/10.1124/pr.112.007138] [PMID: 24076545]
[http://dx.doi.org/10.1074/jbc.M113.458687] [PMID: 23760268]
[http://dx.doi.org/10.1002/syn.10277] [PMID: 14579421]
[http://dx.doi.org/10.1016/j.neuropharm.2004.07.004] [PMID: 15464147]
[http://dx.doi.org/10.1038/258577a0] [PMID: 1207728]
[http://dx.doi.org/10.1073/pnas.73.4.1145] [PMID: 1063395]
[http://dx.doi.org/10.1073/pnas.76.12.6666] [PMID: 230519]
[http://dx.doi.org/10.1111/j.1399-3011.1981.tb01997.x] [PMID: 7287302]
[http://dx.doi.org/10.1038/386499a0] [PMID: 9087409]
[http://dx.doi.org/10.1016/j.peptides.2010.11.013] [PMID: 21126548]
[http://dx.doi.org/10.1111/j.1476-5381.1986.tb10170.x] [PMID: 2869809]
[http://dx.doi.org/10.1016/0014-2999(82)90518-0] [PMID: 7128688]
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb14905.x] [PMID: 7712029]
[http://dx.doi.org/10.1016/S0031-6989(84)80083-1] [PMID: 6522442]
[http://dx.doi.org/10.1073/pnas.89.15.7203] [PMID: 1353890]
[http://dx.doi.org/10.1016/0196-9781(82)90009-2] [PMID: 7177920]
[http://dx.doi.org/10.1016/0306-3623(95)02149-3] [PMID: 8981054]
[http://dx.doi.org/10.1016/0143-4179(85)90036-8] [PMID: 2860597]
[http://dx.doi.org/10.1111/j.1476-5381.1981.tb16797.x] [PMID: 7195758]
[http://dx.doi.org/10.1016/0024-3205(90)90382-2] [PMID: 1972532]
[http://dx.doi.org/10.1016/0006-291X(85)91709-7] [PMID: 2862871]
[PMID: 3612556]
[http://dx.doi.org/10.1248/cpb.39.2316] [PMID: 1804544]
[http://dx.doi.org/10.1111/j.1476-5381.1988.tb16543.x] [PMID: 2905901]
[http://dx.doi.org/10.1021/jm010357t] [PMID: 12408719]
[http://dx.doi.org/10.1016/0006-291X(84)91435-9] [PMID: 6712689]
[http://dx.doi.org/10.1021/jm00123a035] [PMID: 2537427]
[http://dx.doi.org/10.1016/S0223-5234(00)01171-5] [PMID: 11121615]
[http://dx.doi.org/10.1021/jm00392a002] [PMID: 2887656]
[http://dx.doi.org/10.1016/j.ejphar.2007.01.014] [PMID: 17307162]
[http://dx.doi.org/10.1016/j.peptides.2013.10.003] [PMID: 24126280]
[http://dx.doi.org/10.1016/j.peptides.2006.07.006] [PMID: 16919848]
[http://dx.doi.org/10.1124/jpet.102.048561] [PMID: 12606628]
[http://dx.doi.org/10.1016/j.ejphar.2010.10.049] [PMID: 21047509]
[http://dx.doi.org/10.1016/j.ejphar.2013.04.014] [PMID: 23623932]
[http://dx.doi.org/10.1073/pnas.89.6.2046] [PMID: 1347943]
[http://dx.doi.org/10.1007/s00213-010-1946-0] [PMID: 20683583]
[http://dx.doi.org/10.1016/j.bmcl.2011.05.008] [PMID: 21621410]
[http://dx.doi.org/10.1073/pnas.1115231108] [PMID: 22106286]
[http://dx.doi.org/10.1124/jpet.114.213199] [PMID: 24970924]
[http://dx.doi.org/10.1016/j.pain.2014.07.014] [PMID: 25093831]
[http://dx.doi.org/10.1038/srep18198] [PMID: 26657998]
[http://dx.doi.org/10.1073/pnas.0811586106] [PMID: 19273844]
[http://dx.doi.org/10.1172/JCI81070] [PMID: 26011641]
[http://dx.doi.org/10.1213/ANE.0000000000002538] [PMID: 28991118]
[http://dx.doi.org/10.1038/5706] [PMID: 10195199]
[http://dx.doi.org/10.1039/C7CP06745C] [PMID: 29265141]
[http://dx.doi.org/10.1038/nature14886] [PMID: 26245379]
[http://dx.doi.org/10.1038/nature19112] [PMID: 27533032]
[http://dx.doi.org/10.1021/jm300305c] [PMID: 22734622]
[http://dx.doi.org/10.1007/s00894-006-0154-7] [PMID: 17013631]
[http://dx.doi.org/10.1021/jm3012068] [PMID: 23145854]
[http://dx.doi.org/10.1021/acschemneuro.5b00153] [PMID: 26325040]
[http://dx.doi.org/10.1002/syn.21914] [PMID: 27223691]
[http://dx.doi.org/10.1021/acschemneuro.6b00240] [PMID: 27648914]
[PMID: 11303059]