Abstract
Migraine is a neurovascular syndrome associated with a unilateral, throbbing headache accompanied by nausea, vomiting and photo/phonophobia. Several proteins are involved in the etiopathogenesis of migraine headaches. The aim of the present review is to provide an insight into the various target proteins involved in migraine headaches pertaining to the development of a potential anti-migraine drug molecule. Proteins/receptors, such as serotonin (5-HT), Calcitonin Gene-Related Peptide (CGRP), Transient Receptor Potential Vanilloid 1 (TRPV1), cannabinoid, glutamate, opioid, and histamine receptors play various roles in migraine. The nature of the proteins, their types, binding partner membrane proteins and the consequences of the reactions produced have been discussed. The studies conducted on animals and humans with the above-mentioned target proteins/receptors and the results obtained have also been reviewed.
Calcitonin Gene-Related Peptide (CGRP), a G protein-coupled receptor (GPCR), significantly contributes to the progression of migraine. CGRP antagonist inhibits the release of CGRP from trigeminal neurons of the trigeminal ganglion. Based on the study results, the present review suggests that the inhibition of the CGRP receptor might be a successful way to treat migraine headaches. Currently, researchers across the world are focusing their attention towards the development of novel molecules to treat migraine headaches by targeting the CGRP receptor, which can be attributed to its specificity among the several proteins involved in migraine.
Keywords: Migraine, target proteins, GPCR, CGRP release, trigeminal vascular system, anti-migraine drugs.
Graphical Abstract
[http://dx.doi.org/10.1111/j.1526-4610.2005.4501001.x] [PMID: 15833088]
[http://dx.doi.org/10.1111/j.1526-4610.2012.02265.x] [PMID: 23078241]
[http://dx.doi.org/10.1038/nrn1102] [PMID: 12728266]
[http://dx.doi.org/10.1111/j.1526-4610.2006.00309.x] [PMID: 16412147]
[http://dx.doi.org/10.1001/jama.295.15.1824] [PMID: 16622144]
[http://dx.doi.org/10.1172/JCI5347] [PMID: 9927501]
[http://dx.doi.org/10.1016/j.ijsu.2015.07.710] [PMID: 26283296]
[http://dx.doi.org/10.1097/00002508-200307000-00009] [PMID: 12840620]
[http://dx.doi.org/10.1016/0304-3959(93)90057-V] [PMID: 8316392]
[http://dx.doi.org/10.1111/j.1526-4610.2006.00322.x] [PMID: 16412153]
[http://dx.doi.org/10.1046/j.1468-2982.2003.00544.x] [PMID: 12780762]
[http://dx.doi.org/10.1073/pnas.0306147101] [PMID: 15016917]
[PMID: 18100415]
[PMID: 18139191]
[PMID: 8700126]
[http://dx.doi.org/10.1016/S0304-3940(98)00680-6] [PMID: 9779933]
[http://dx.doi.org/10.1073/pnas.91.9.3666] [PMID: 8170966]
[http://dx.doi.org/10.1016/0028-3908(94)90067-1] [PMID: 7984275]
[http://dx.doi.org/10.1007/BF00168556] [PMID: 8584041]
[http://dx.doi.org/10.1038/sj.bjp.0702773] [PMID: 10578124]
[http://dx.doi.org/10.1046/j.1468-2982.1999.019004248.x] [PMID: 10376171]
[http://dx.doi.org/10.1001/archneur.59.7.1084] [PMID: 12117355]
[http://dx.doi.org/10.1016/S0165-0173(00)00048-5] [PMID: 11245884]
[http://dx.doi.org/10.1056/NEJMp048016] [PMID: 15014178]
[http://dx.doi.org/10.1111/j.1468-2982.2003.00719.x] [PMID: 15265049]
[http://dx.doi.org/10.1097/00001756-199707070-00029] [PMID: 9243618]
[http://dx.doi.org/10.1021/jm0155190] [PMID: 11708905]
[http://dx.doi.org/10.1021/jm030020m] [PMID: 12825944]
[http://dx.doi.org/10.1007/s002109900045] [PMID: 10494882]
[http://dx.doi.org/10.1186/1129-2377-14-S1-P77]
[http://dx.doi.org/10.1016/0028-3908(89)90040-3] [PMID: 2526302]
[http://dx.doi.org/10.1016/0014-2999(89)90137-4] [PMID: 2612565]
[http://dx.doi.org/10.1007/BF00614305] [PMID: 3709648]
[http://dx.doi.org/10.1046/j.1468-2982.2000.00069.x] [PMID: 11037741]
[http://dx.doi.org/10.1016/j.vph.2005.07.001] [PMID: 16099727]
[http://dx.doi.org/10.1016/j.sigm.2005.10.002]
[http://dx.doi.org/10.1007/s001340050894] [PMID: 10401952]
[http://dx.doi.org/10.1159/000085061] [PMID: 15920337]
[http://dx.doi.org/10.1016/S0165-6147(00)01555-8] [PMID: 11121574]
[http://dx.doi.org/10.1124/pr.54.2.233] [PMID: 12037140]
[http://dx.doi.org/10.1038/298240a0] [PMID: 6283379]
[http://dx.doi.org/10.1046/j.1468-2982.1996.1605310.x] [PMID: 8869765]
[http://dx.doi.org/10.1038/304129a0] [PMID: 6346105]
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb22759.x] [PMID: 1322107]
[http://dx.doi.org/10.1016/S0149-7634(96)00023-1] [PMID: 9353797]
[http://dx.doi.org/10.1016/S0165-6147(00)91555-4] [PMID: 11426419]
[http://dx.doi.org/10.1210/edrv-17-5-533] [PMID: 8897024]
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb22766.x] [PMID: 1637083]
[http://dx.doi.org/10.1038/30666] [PMID: 9620797]
[http://dx.doi.org/10.1042/bst0300451] [PMID: 12196113]
[http://dx.doi.org/10.1093/molehr/6.9.811] [PMID: 10956553]
[http://dx.doi.org/10.1038/sj.bjp.0703655] [PMID: 11053206]
[http://dx.doi.org/10.1016/0006-8993(87)90074-6] [PMID: 2435372]
[http://dx.doi.org/10.1074/jbc.M211379200] [PMID: 12707285]
[http://dx.doi.org/10.1046/j.1468-2982.1997.1703166.x] [PMID: 9170339]
[http://dx.doi.org/10.1016/S0028-3908(02)00008-4] [PMID: 11955527]
[http://dx.doi.org/10.1021/jm0490641] [PMID: 16161996]
[http://dx.doi.org/10.1016/j.nurt.2010.02.004]
[http://dx.doi.org/10.1212/WNL.0b013e3181b87942] [PMID: 19770473]
[PMID: 14018711]
[http://dx.doi.org/10.1016/j.tins.2007.03.004] [PMID: 17397938]
[http://dx.doi.org/10.1016/0006-8993(79)90391-3] [PMID: 455093]
[http://dx.doi.org/10.1212/WNL.40.11.1660] [PMID: 2234421]
[http://dx.doi.org/10.1002/ana.21077] [PMID: 17387726]
[http://dx.doi.org/10.1016/j.mehy.2005.09.045] [PMID: 16298497]
[http://dx.doi.org/10.1111/j.1526-4610.1994.hed3409536.x] [PMID: 8002329]
[http://dx.doi.org/10.1046/j.1468-2982.1998.1804174.x] [PMID: 9642491]
[http://dx.doi.org/10.1212/WNL.51.3.781] [PMID: 9748026]
[http://dx.doi.org/10.1111/j.1468-1331.2010.02988.x] [PMID: 20236178]
[http://dx.doi.org/10.1046/j.1468-2982.2000.00001.x] [PMID: 10817442]
[http://dx.doi.org/10.1046/j.1526-4610.2002.02105.x]
[http://dx.doi.org/10.1007/s100720300005] [PMID: 12624717]
[http://dx.doi.org/10.1053/ajem.2002.30007] [PMID: 11781912]
[http://dx.doi.org/10.1016/S0735-6757(99)90096-7] [PMID: 10452443]
[http://dx.doi.org/10.1096/fasebj.9.7.7737460] [PMID: 7737460]
[http://dx.doi.org/10.1002/acn3.66] [PMID: 25328905]
[http://dx.doi.org/10.1100/tsw.2007.230] [PMID: 17982582]
[http://dx.doi.org/10.1111/bph.12591] [PMID: 24467301]
[http://dx.doi.org/10.1007/BF02042625] [PMID: 6099346]
[http://dx.doi.org/10.1172/JCI119506] [PMID: 9202066]
[http://dx.doi.org/10.1073/pnas.91.10.4219] [PMID: 7910403]
[http://dx.doi.org/10.1111/j.1526-4610.1992.hed3207348.x] [PMID: 1526766]
[http://dx.doi.org/10.1021/ja01062a046]
[PMID: 3018800]
[http://dx.doi.org/10.1073/pnas.87.5.1932] [PMID: 2308954]
[http://dx.doi.org/10.1523/JNEUROSCI.11-02-00563.1991] [PMID: 1992016]
[http://dx.doi.org/10.1016/S0306-4522(97)00436-3] [PMID: 9460749]
[http://dx.doi.org/10.1124/pr.54.2.161] [PMID: 12037135]
[http://dx.doi.org/10.1016/S0005-2760(98)00042-3] [PMID: 9630590]
[http://dx.doi.org/10.1385/NMM:7:1-2:037] [PMID: 16052037]
[http://dx.doi.org/10.1038/nm1561] [PMID: 17401376]
[http://dx.doi.org/10.1080/02791072.1988.10524365] [PMID: 3392635]
[http://dx.doi.org/10.1073/pnas.90.16.7656] [PMID: 8395053]
[PMID: 7565624]
[http://dx.doi.org/10.1152/jn.1997.78.1.43] [PMID: 9242259]
[http://dx.doi.org/10.1523/JNEUROSCI.15-10-06552.1995] [PMID: 7472417]
[http://dx.doi.org/10.1016/0091-3057(93)90230-Q] [PMID: 7906042]
[PMID: 8035318]
[http://dx.doi.org/10.1124/jpet.106.106971] [PMID: 17018694]
[http://dx.doi.org/10.1016/j.neulet.2009.06.021] [PMID: 19539700]
[http://dx.doi.org/10.1016/j.expneurol.2010.03.029] [PMID: 20353780]
[http://dx.doi.org/10.1124/jpet.103.059808] [PMID: 14718591]
[http://dx.doi.org/10.1186/1129-2377-15-14] [PMID: 24636539]
[http://dx.doi.org/10.1177/0333102413499646] [PMID: 23935158]
[http://dx.doi.org/10.1007/BF01046588] [PMID: 1684179]
[http://dx.doi.org/10.1016/0304-3940(92)90339-9]
[http://dx.doi.org/10.1124/pr.109.002451] [PMID: 20716669]
[http://dx.doi.org/10.2174/138920111798357438] [PMID: 21466446]
[http://dx.doi.org/10.1212/01.wnl.0000306315.03021.2a] [PMID: 18347319]
[http://dx.doi.org/10.1016/0166-2236(91)90022-M] [PMID: 1708538]
[http://dx.doi.org/10.1152/ajpheart.00523.2001] [PMID: 11893577]
[http://dx.doi.org/10.1038/nn980] [PMID: 12469126]
[http://dx.doi.org/10.1038/nrn1387] [PMID: 15100718]
[http://dx.doi.org/10.1038/90507] [PMID: 11477426]
[http://dx.doi.org/10.1038/nn1623] [PMID: 16388306]
[http://dx.doi.org/10.1111/j.1526-4610.2008.01262.x] [PMID: 19125874]
[http://dx.doi.org/10.1001/archneurpsyc.1941.02280200137007]
[http://dx.doi.org/10.1038/nrneurol.2013.192] [PMID: 24042483]
[http://dx.doi.org/10.1046/j.1468-2982.1997.1706652.x] [PMID: 9350385]
[http://dx.doi.org/10.1177/033310240102100704] [PMID: 11595007]
[PMID: 7512795]
[http://dx.doi.org/10.1113/jphysiol.1982.sp014220] [PMID: 6288930]
[http://dx.doi.org/10.1016/S0006-8993(00)02630-5] [PMID: 10967305]
[http://dx.doi.org/10.1016/S0306-4522(98)00536-3] [PMID: 10338304]
[http://dx.doi.org/10.1111/j.1468-2982.2004.00723.x] [PMID: 15196302]
[PMID: 10027832]
[http://dx.doi.org/10.1111/j.1528-1157.2000.tb02173.x] [PMID: 10768302]
[http://dx.doi.org/10.1111/j.1468-2982.2007.01326.x] [PMID: 17441971]
[http://dx.doi.org/10.1007/s40265-014-0262-0] [PMID: 25030431]
[http://dx.doi.org/10.1046/j.1468-2982.1997.1702109.x] [PMID: 9137848]
[http://dx.doi.org/10.1046/j.1526-4610.43.7s.4.x]
[http://dx.doi.org/10.1111/j.1526-4610.2010.01678.x] [PMID: 20487038]
[http://dx.doi.org/10.1016/j.neuropharm.2014.04.018] [PMID: 24796257]
[http://dx.doi.org/10.1212/WNL.0b013e3182824e66] [PMID: 23365053]
[http://dx.doi.org/10.1212/WNL.55.1.139] [PMID: 10891926]
[http://dx.doi.org/10.1038/39807] [PMID: 9349813]
[http://dx.doi.org/10.1007/s00424-005-1423-5] [PMID: 15909179]
[http://dx.doi.org/10.1016/S0968-0004(99)01426-7] [PMID: 10431175]
[http://dx.doi.org/10.1111/j.1526-4610.2011.02053.x] [PMID: 22289052]
[http://dx.doi.org/10.1016/0306-4522(88)90064-4] [PMID: 3288903]
[http://dx.doi.org/10.1124/jpet.102.046250] [PMID: 12604668]
[http://dx.doi.org/10.2174/138161208783330754] [PMID: 18220816]
[http://dx.doi.org/10.1016/0166-2236(94)90149-X] [PMID: 7532332]
[http://dx.doi.org/10.1016/S0896-6273(00)80564-4] [PMID: 9768840]
[http://dx.doi.org/10.1038/22761] [PMID: 10440374]
[http://dx.doi.org/10.1073/pnas.97.11.6155] [PMID: 10823958]
[http://dx.doi.org/10.1038/sj.emboj.7600784] [PMID: 16107881]
[http://dx.doi.org/10.1016/S0896-6273(00)80813-2] [PMID: 10433272]
[http://dx.doi.org/10.1038/35082088] [PMID: 11418861]
[http://dx.doi.org/10.1073/pnas.122196999] [PMID: 12060783]
[http://dx.doi.org/10.1186/1744-8069-1-3] [PMID: 15813989]
[http://dx.doi.org/10.1523/JNEUROSCI.5403-05.2006] [PMID: 16793879]
[PMID: 1852779]
[PMID: 10353985]
[http://dx.doi.org/10.1523/JNEUROSCI.18-16-06081.1998] [PMID: 9698303]
[http://dx.doi.org/10.1046/j.1460-9568.2000.00218.x] [PMID: 10998108]
[http://dx.doi.org/10.1152/jn.00748.2002] [PMID: 12612039]
[http://dx.doi.org/10.1111/j.1468-2982.2007.01448.x] [PMID: 17888011]
[http://dx.doi.org/10.1016/j.ejphar.2006.04.046] [PMID: 16737693]
[http://dx.doi.org/10.1186/s10194-015-0539-z] [PMID: 26109436]
[http://dx.doi.org/10.1186/1741-7015-7-71] [PMID: 19917094]
[http://dx.doi.org/10.1038/sj.bjp.0705486] [PMID: 14534154]
[http://dx.doi.org/10.1016/S1090-3801(09)60705-9]
[http://dx.doi.org/10.1002/jemt.1085] [PMID: 11301496]
[http://dx.doi.org/10.1016/j.brainresrev.2004.11.006] [PMID: 15960987]
[http://dx.doi.org/10.1038/nature01324] [PMID: 12490961]
[http://dx.doi.org/10.1016/S1357-2725(03)00208-5] [PMID: 12962699]
[http://dx.doi.org/10.1056/NEJMcibr023206] [PMID: 12711748]
[http://dx.doi.org/10.1034/j.1600-065X.2000.917305.x] [PMID: 10719674]
[http://dx.doi.org/10.1152/physrev.1997.77.4.1033] [PMID: 9354811]
[http://dx.doi.org/10.1002/ddr.20208]
[http://dx.doi.org/10.1111/j.1471-4159.1984.tb05416.x] [PMID: 6491664]
[http://dx.doi.org/10.1007/BF01252276] [PMID: 1869885]
[http://dx.doi.org/10.1016/j.bbrc.2014.07.124] [PMID: 25094046]
[http://dx.doi.org/10.1111/j.1476-5381.1997.tb06811.x] [PMID: 9142412]
[http://dx.doi.org/10.1124/mol.55.6.1101] [PMID: 10347254]
[http://dx.doi.org/10.1074/jbc.M006480200] [PMID: 10973974]
[http://dx.doi.org/10.1007/BF00202867] [PMID: 8045566]
[http://dx.doi.org/10.1073/pnas.88.2.429] [PMID: 1703298]
[http://dx.doi.org/10.1006/bbrc.2000.4008] [PMID: 11118334]
[http://dx.doi.org/10.1212/WNL.25.7.681] [PMID: 239368]
[http://dx.doi.org/10.1038/jcbfm.1981.49] [PMID: 7328153]
[http://dx.doi.org/10.1038/302832a0] [PMID: 6188956]
[http://dx.doi.org/10.1016/0304-3959(88)90012-7] [PMID: 7402688]
[http://dx.doi.org/10.1152/ajplegacy.1971.221.6.1629] [PMID: 5124307]
[PMID: 2106796]
[http://dx.doi.org/10.1038/sj.bjp.0701097] [PMID: 9146885]
[http://dx.doi.org/10.1016/0009-9236(95)90074-8] [PMID: 7628185]
[http://dx.doi.org/10.1046/j.1468-2982.1997.1703175.x] [PMID: 9170340]
[PMID: 6115052]
[http://dx.doi.org/10.1046/j.1468-2982.2003.00586.x] [PMID: 14616929]
[http://dx.doi.org/10.1097/00005392-199503000-00021] [PMID: 7861501]
[http://dx.doi.org/10.1001/archneur.1979.00500470065013] [PMID: 508127]
[http://dx.doi.org/10.1016/j.clineuro.2004.03.004] [PMID: 15567552]
[http://dx.doi.org/10.1016/S0196-0644(98)70126-X] [PMID: 9701293]