Migraine headache is the first neurological condition treatable by a drug targeted to a specific receptor binding site. Originally viewed as a disorder of brain blood vessels, migraine may have as its biological basis a disturbance in brain function. Regarding therapy, recent molecular data document that 5-HT1D receptors on primary afferent fibers are coupled to inhibition of neuropeptide release, blockade of neurogenic inflammation, and c-fos expression within the trigeminal nucleus caudalis after noxious meningeal stimulation in experimental animals. The 5-HT1Dα receptor subtype (as opposed to the 5-HT 1Dβ receptor) has emerged as an important therapeutic target aimed at blocking trigeminal nerve fibers without constricting vascular smooth muscle. NEUROSCIENTIST 2:191-200, 1996
Ray BS, Wolff HGExperimental studies on headache: pain sensitive structures of the head and their significance in headache. Arch Surg1940;41:813-856.
2.
Wolff HGHeadache and other head pain. New York: Oxford University Press1972.
3.
von Luschka H.Die Nerven in der harten Hirnhaut Tübingen: Laupp 1850.
4.
Mayberg M., Langer RS, Zervas NT, Moskowitz MAPerivascular meningeal projections from cat trigeminal ganglia: possible pathway for vascular headaches in man. Science1981 ,213.228-230.
5.
Graham JR, Wolff HGMechanisms of migraine headache and action of ergotamme tartrate. Arch Neurol Psychiatry1938;39: 737-763.
Ferran M.Sumatnptan International Study Group. Treatment of migraine attacks with sumatriptan . N Engl J Med1991;325:316-321.
8.
Mayberg MR, Zervas NT, Moskowitz MATrigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry. J Comp Neurol1984; 223:46-56.
9.
O'Connor TP, van der Kooy D.Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries. J Neurosci1988;8: 2468-2476.
10.
Liu-Chen L-Y. , Mayberg MR, Moskowitz MAImmunohistochemical evidence for a substance P-containing trigeminovascular pathway to pial arteries in cats. Brain Res1983;268:162-166.
11.
Liu-Chen L-Y. , Han DH, Moskowitz MAPia arachnoid contains substance P originating from trigeminal neurons. Neuroscience1983 ;9:803-808.
12.
McCullouch J., Uddman R., Kmgman TA, Edvmsson L.Calcitonin gene-related peptide. functional role in cerebrovascular regulation. Proc Natl Acad Sci U S A1986;83:5731-5735.
13.
Liu-Chen L-Y. , Liszczak TM, King JC, Moskowitz MAImmunoelectron microscopic study of substance P-containing fibers in feline cerebral arteries . Brain Res1986;369:12-20.
14.
Sluka KA, Willis WD, Westlund KNInflammation-induced release of excitatory ammo acid is prevented by spinal administration of a GABAA but not by a GABAB receptor antagonist in rats. J Pharmacol Exp Ther1994 ;271;76-82.
15.
Markowitz S. , Saito K., Moskowitz MANeurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not bram. J Neurosci1987;7:4129-4136.
16.
Dimitriadou V., Buzzi MG, Moskowitz MA, Theohandes TCTngeminal sensory fiber stimulation induces morphological changes reflecting secretion in rat dura mater mast cells. Neuroscience1991;44:97-112.
17.
Dimitriadou V., Buzzi MG, Theoharides TC, Moskowitz MAUltrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation. Neuroscience1992;48:187-203.
18.
Moskowitz MANeurogenic versus vascular mechanisms of sumatnptan and ergot alkaloids m migraine. Trends Pharmacol Sci1992;13:307-311
19.
Goadsby PJ, Edvmsson L.Sumatriptan reverses the changes in CGRP seen in the headache phase of migraine . Cephalalgia1991; 11 Suppl 11:3.
20.
Buzzi MG, Dimitnadou V., Theohandes TC, Moskowitz MA5-Hydroxytryptamine receptor agonists for the abortive treatment of vascular headaches block mast cell, endothelial and platelet activation within the rat dura mater after trigeminal stimulation. Brain Res1992;583-137-149.
21.
Buzzi MG, Moskowitz MAThe antimigraine drug, sumatriptan (GR43175), specifically blocks neurogenic plasma extravasation from blood vessels in rat dura mater. Br J Pharmacol1990;99: 202-206.
22.
Heunng RE, Peroutka SJCharacterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci1987 ;7.894-903.
23.
Beer MS, Middlemiss DN, McAllister G. 5-HT1-like receptor: six down and still counting . Trends Pharmacol Sci1993;14:228-231.
24.
Zifa E., Fillion G.5-hydroxytryptamine receptors. Pharmacol Rev1992;44:401-458.
25.
Brumvels AT , Lery H., Nozulak J., Palacios JM, Hoyer D.5-HT1D binding sites in various species: similar pharmacological profile in calf, guinea-pig, dog, monkey and human brain membranes. Naunyn Schmiedebergs Arch Pharmacol1992;346:243-248.
26.
Hartig PR, Branchek TA, Weinshank RLA subfamily of 5-HT1D receptor genes. Trends Pharmacol Sci1992;13;152-159.
27.
Plassat J-L. , Boschert U., Amlaiky N., Hen R.The mouse 5-HT 5 receptor reveals a remarkable heterogeneity within the 5-HT1D receptor family. EMBO J1992;11:4779-4786.
28.
Humphrey Ppa , Hartig P., Hoyer D.A proposed new nomenclature for 5-HT receptors . Trends Pharmacol Sci1993; 14:233-236.
29.
VanSade J., Allgeier A., Massart C., et al. The human and dog 5-HT1D receptors can both activate and inhibit adenylate cyclase in transfected cells. Eur J Pharmacol Mol Pharmacol Sect1993;247: 177-184.
30.
Zgombick JM , Borden LA, Cochran TL, Kucharewicz SA, Wemshank RL, Branchek TADual coupling of cloned human 5-hydroxytryptamine 1Dα and 5-hydroxytryptamine 1Dβ receptors in stably transfected fibroblasts: inhibition of adenylate cyclase and elevation of intracellular calcium concentrations via pertussis toxin-sensitive G protein(s . Mol Pharmacol1993;44:575.
31.
Hamel E., Fan E., Linville D., Ting V., Villemure J-G, Chia L-S. Expression of mRNA for the serotonin 5-hydroxytryptamine 1Dα receptor subtype in human and bovine cerebral arteries. Mol Pharmacol1993;44:242-246.
32.
Limberger N. , Deicher R., Starke K.Species differences in presynaptic serotonin autoreceptors: mainly 5-HT1B but possibly m addition 5-HT 1D in the rat, 5-HT1D in the rabbit and guinea-pig brain cortex. Naunyn Schmiedebergs Arch Pharmacol1991;343:353-364.
33.
Brumvels AT , Landwehrmeyer B., Gustafson EL, et al. Localization of 5-HT1B, 5-HT1Dα, 5-HT1E and 5-HT 1F receptor messenger RNA in rodent and primate bram. Neuropharmacology1994;33: 367-386.
34.
Saito K., Markowitz S., Moskowitz MAErgot alkaloids block the neurogenic extravasation in dura mater: proposed action in vascular headaches. Ann Neurol1988 ;24:732-737.
35.
Schoeffter P. , Hoyer D.5-Hydroxytryptamine (5-HT) induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype. J Pharmacol Exp Ther1990;252;387-395.
36.
Gupta P.An endothelial 5-HT receptor that mediates relaxation in guinea-pig isolated jugular vein resembles the 5-HT1D subtypeBr J Pharmacol1992;106:703-709.
37.
Yu X-J., Waeber C., Castanon N., Scearce K., Hen R., Macor JE, Chauveau J., Moskowitz MA5-carboxamido-tryptamine, CP-122, 288 and dihydroergotamine, but not sumatriptan, CP-93,129 or serotonin-5-O-carboxymethyl-glycyltyrosinamide block dural plasma protein extravasation in knockout mice that lack 5-hydroxytryptamine 1B receptors. Mol Pharmacol1996;49:in press
38.
Saudou F., Amara DA, Diench A., et al. Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science1994;265:1875-1878.
39.
Buzzi MG, Carter WB, Shimizu T., Heath H. III, Moskowitz MADihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion . Neuropharmacology1991;30:1193-1200.
40.
Feniuk W., Humphrey Ppa, Perren MJ The selective carotid arterial vasoconstrictor action of GR43175 in anaesthetized dogs. Br J Pharmacol1989 ;96:83-90.
41.
Humphrey Ppa , Femuk W., Perren MJ, Beresford Ijm, Skmgle M.Serotonin and migraine. Ann NY Acad Sci1990;600:587-600.
42.
Kaube H., Hoskm KL, Goadsby PJInhibition by sumatriptan of central trigeminal neurons only after blood-brain bamer disruption. Br J Pharmacol1993;109:788-792.
43.
Waeber C., Moskowitz MA[3H]sumatriptan labels both 5-HT1D and 5-HT1F receptor binding sites in the guinea pig brain: an autoradiographic studyNaunyn Schmiedebergs Arch Pharmacol1995 ;352263-275
44.
Matsubara T. , Moskowitz MA, Huang Z.UK-14,304, R(-)-α-methyl-histamme and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanismsEur J Pharmacol1992;224:145-150
45.
Buzzi MG, Sakas DE, Moskowitz MAIndomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura materEur J Pharmacol1989;165:251-258.
46.
Rebeck GW, Maynard KI, Hyman B., Moskowitz MA Selective 5-HT1Dα receptor gene expression in trigeminal ganglia: implications for anti-migraine drug development. Proc Natl Acad Sci U S A1994;91:3666-3669.
47.
Nozaki K., Boccalini P., Moskowitz MAExpression of c-fos-like immunoreactivity in bramstem after meningeal imtation by blood in the subarachnoid space. Neuroscience1992;49:669-680.
48.
Nozaki K., Moskowitz MA, Boccalini P.CP-93,129, sumatriptan, dihydroergotamine block c-fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the menmges . Br J Pharmacol1992;106:409-415.
49.
Jensen R., Brinck T., Olesen J.Sodium valproate has a prophylactic effect in migraine with aura: a triple-blind, placebo-controlled crossover study. Neurology1994;44:647-651.
50.
Lee WS, Limmroth V., Cutrer FM, Waeber C., Moskowitz MAPeripheral GABAA receptor mediated effects of sodium valproate on dural plasma protein extravasation to substance P and tngemmal stimulation . Br J Pharmacol1995;116:1661-1667.
51.
Limmroth V. , Lee WS, Moskowitz MAGABAA-receptor mediated effects of progesterone, its ring A-reduced metabolites and synthetic neuroactive steroids on neurogenic edema in the rat menmges. Br J Pharmacol1996;117:99-104.
52.
Cutrer FM, Limmroth V., Ayata G., Moskowitz MAAttentuation by valproate of c-fos immunoreactivity in trigeminal nucleus caudahs induced by intracisternal capsaicin. Br J Pharmacol1995; 116:3199-3204.
53.
Kraig RP, Dong L., Thisted R., Jaeger CBSpreading depression increases immunohistochemical staining of glial fibrillary acidic protein. J Neurosci1991 ;11:2187-2198.
54.
Moskowitz MA , Nozaki K., Kraig RPNeocortical spreading depression provokes the expresion of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms. J Neurosci1993;13:1167-1177.
55.
Lauritzen M. , Hansen AK, Kronborg D., Wieloch T.Cortical spreading depression is associated with arachidonic acid accumulation and preservation of energy charge. J Cereb Blood Flow Metab1990,10:115-122.
56.
Woods RP, Iacoboni M., Mazziotta JCBrief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache. N Engl J Med1994;331:1689-1692.
57.
Bradley PB, Engel G., Femuk W., et al. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology1986;25:563-576.
58.
Hoyer D., Clarke DE, Fozard JR, et al VII. International Union of Pharmacology classification of receptors for 5-hydroxytryptamme (serotonin. Pharmacol Rev1994;46.157-203.
