Compounds > mk-6096
Page last updated: 2024-11-13

mk-6096

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

MK-6096: antagonist of orexin receptors 1 and 2; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID25128145
CHEMBL ID2107822
SCHEMBL ID1716633
MeSH IDM0575644

Synonyms (38)

Synonym
mk 6096
mk6096
mk-6096
[(2r,5r)-5-[(5-fluoropyridin-2-yl)oxymethyl]-2-methylpiperidin-1-yl]-(5-methyl-2-pyrimidin-2-ylphenyl)methanone
filorexant
gtpl4460
CHEMBL2107822
1088991-73-4
filorexant [usan:inn]
e6btt8va5z ,
unii-e6btt8va5z
methanone, ((2r,5r)-5-(((5-fluoro-2-pyridinyl)oxy)methyl)-2-methyl-1-piperidinyl)(5-methyl-2-(2-pyrimidinyl)phenyl)-
((2r,5r)-5-(((5-fluoropyridin-2-yl)oxy)methyl)-2-methylpiperidin-1-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone
bdbm104692
D10345
us8569311, e-5
filorexant (usan)
filorexant [who-dd]
filorexant [usan]
[(2r,5r)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl][5-methyl-2-(pyrimidin-2-yl)phenyl]methanone
filorexant [inn]
CS-4437
SCHEMBL1716633
HY-15653
DTXSID50148764
AKOS027323764
NCGC00484077-01
filorexant(mk-6096)
methanone, [(2r,5r)-5-[[(5-fluoro-2-pyridinyl)oxy]methyl]-2-methyl-1-piperidinyl][5-methyl-2-(2-pyrimidinyl)phenyl]-
DB12158
mk-6096; filorexant
mfcd28100674
EX-A2101
[(2~{r},5~{r})-5-[(5-fluoranylpyridin-2-yl)oxymethyl]-2-methyl-piperidin-1-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)methanone
NT5 ,
Q18355303
AC-35933
AS-82282

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
" MK-6096 is an orally bioavailable potent and selective reversible antagonist of OX(1)R and OX(2)R currently in clinical development for insomnia."( Pharmacological characterization of MK-6096 - a dual orexin receptor antagonist for insomnia.
Breslin, MJ; Coleman, PJ; Cox, CD; Cui, D; Doran, SM; Fox, SV; Garson, SL; Gotter, AL; Harrell, CM; Reiss, DR; Renger, JJ; Schreier, JD; Stevens, J; Tannenbaum, PL; Winrow, CJ, 2012)		1.56
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)		0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Orexin receptor type 1Homo sapiens (human)IC50 (µMol)0.01350.00600.04450.1990AID1190417; AID1279957
Orexin receptor type 1Homo sapiens (human)Ki0.00210.00030.28763.1623AID1190415; AID1237020; AID1279994; AID1582239; AID765089
Orexin receptor type 2Homo sapiens (human)IC50 (µMol)0.01400.00040.51858.1000AID1190416; AID1280008
Orexin receptor type 2Homo sapiens (human)Ki0.00030.00020.37713.7810AID1190414; AID1237021; AID1279993; AID1582240; AID765090
Sigma non-opioid intracellular receptor 1Rattus norvegicus (Norway rat)Ki0.00030.00030.26715.0700AID765090
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (10)

Processvia Protein(s)Taxonomy
neuropeptide signaling pathwayOrexin receptor type 1Homo sapiens (human)
chemical synaptic transmissionOrexin receptor type 1Homo sapiens (human)
feeding behaviorOrexin receptor type 1Homo sapiens (human)
regulation of cytosolic calcium ion concentrationOrexin receptor type 1Homo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeOrexin receptor type 1Homo sapiens (human)
cellular response to hormone stimulusOrexin receptor type 1Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayOrexin receptor type 2Homo sapiens (human)
neuropeptide signaling pathwayOrexin receptor type 2Homo sapiens (human)
chemical synaptic transmissionOrexin receptor type 2Homo sapiens (human)
feeding behaviorOrexin receptor type 2Homo sapiens (human)
regulation of circadian sleep/wake cycle, wakefulnessOrexin receptor type 2Homo sapiens (human)
circadian sleep/wake cycle processOrexin receptor type 2Homo sapiens (human)
locomotionOrexin receptor type 2Homo sapiens (human)
regulation of cytosolic calcium ion concentrationOrexin receptor type 2Homo sapiens (human)
cellular response to hormone stimulusOrexin receptor type 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (6)

Processvia Protein(s)Taxonomy
G protein-coupled receptor activityOrexin receptor type 1Homo sapiens (human)
protein bindingOrexin receptor type 1Homo sapiens (human)
orexin receptor activityOrexin receptor type 1Homo sapiens (human)
peptide hormone bindingOrexin receptor type 1Homo sapiens (human)
peptide bindingOrexin receptor type 1Homo sapiens (human)
protein bindingOrexin receptor type 2Homo sapiens (human)
neuropeptide receptor activityOrexin receptor type 2Homo sapiens (human)
orexin receptor activityOrexin receptor type 2Homo sapiens (human)
peptide hormone bindingOrexin receptor type 2Homo sapiens (human)
peptide bindingOrexin receptor type 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
plasma membraneOrexin receptor type 1Homo sapiens (human)
synapseOrexin receptor type 1Homo sapiens (human)
plasma membraneOrexin receptor type 1Homo sapiens (human)
plasma membraneOrexin receptor type 2Homo sapiens (human)
synapseOrexin receptor type 2Homo sapiens (human)
plasma membraneOrexin receptor type 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (36)

Assay IDTitleYearJournalArticle
AID1280006Oral bioavailability in dog2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1280005Oral bioavailability in rat2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID765089Binding affinity to orexin receptor 1 (unknown origin)2013Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17
Selective orexin receptor antagonists.
AID1279994Binding affinity to OX1R (unknown origin)2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1279956Effect on sleep parameter in po dosed rat by EEG analysis2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID765090Binding affinity to orexin receptor 2 (unknown origin)2013Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17
Selective orexin receptor antagonists.
AID1190414Antagonist activity at human OX2R by radioligand displacement assay2015Bioorganic & medicinal chemistry letters, Feb-01, Volume: 25, Issue:3
Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant.
AID1280007Effect on sleep parameter in po dosed dog by EEG analysis2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1280001Clearance in iv dosed rat2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1280000Receptor occupancy at OX2R in rat brain assessed as drug level in plasma2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1190417Antagonist activity at human OX1R by FLIPR assay2015Bioorganic & medicinal chemistry letters, Feb-01, Volume: 25, Issue:3
Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant.
AID1190415Antagonist activity at human OX1R by radioligand displacement assay2015Bioorganic & medicinal chemistry letters, Feb-01, Volume: 25, Issue:3
Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant.
AID1237021Antagonist activity at orexin-2 receptor (unknown origin)2015Bioorganic & medicinal chemistry letters, Aug-01, Volume: 25, Issue:15
Recent trends in orexin research--2010 to 2015.
AID1280008Antagonist activity at human OX2R expressed in CHO cell membranes assessed as inhibition of orexin-A-induced intracellular calcium release after 120 mins2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1237020Antagonist activity at orexin-1 receptor (unknown origin)2015Bioorganic & medicinal chemistry letters, Aug-01, Volume: 25, Issue:15
Recent trends in orexin research--2010 to 2015.
AID1582240Displacement of [3H]4-(2,6-Difluoro-4-methoxybenzyl)-2-(5,6-dimethoxypyridin-3-yl)-2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide from human wild-type OX2 receptor expressed in baculovirus infected Sf21 insect cell membranes measured after 90 mins by liqu2020Journal of medicinal chemistry, 02-27, Volume: 63, Issue:4
Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis.
AID1280003Clearance in iv dosed dog2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1582239Displacement of [3H]4-(2,6-Difluoro-4-methoxybenzyl)-2-(5,6-dimethoxypyridin-3-yl)-2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide from human wild-type OX1 receptor expressed in baculovirus infected Sf21 insect cell membranes measured after 90 mins by liqu2020Journal of medicinal chemistry, 02-27, Volume: 63, Issue:4
Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis.
AID1279997Plasma protein binding in rat2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1190418Selectivity ratio of Ki for human OX1R to Ki for human OX2R2015Bioorganic & medicinal chemistry letters, Feb-01, Volume: 25, Issue:3
Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant.
AID1280009Ratio of drug level in CSF to plasma in rat2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1279957Antagonist activity at human OX1R expressed in CHO cell membranes assessed as inhibition of orexin-A-induced intracellular calcium release after 120 mins2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1190416Antagonist activity at human OX2R by FLIPR assay2015Bioorganic & medicinal chemistry letters, Feb-01, Volume: 25, Issue:3
Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant.
AID1279986Plasma protein binding in human2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1280002Half life in iv dosed rat2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1280004Half life in iv dosed dog2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1279993Binding affinity to OX2R (unknown origin)2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1280010Ratio of drug level in brain to plasma in rat2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1279998Plasma protein binding in dog2016Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2
Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346418Human OX2 receptor (Orexin receptors)2012Neuropharmacology, Feb, Volume: 62, Issue:2
Pharmacological characterization of MK-6096 - a dual orexin receptor antagonist for insomnia.
AID1346381Human OX1 receptor (Orexin receptors)2012Neuropharmacology, Feb, Volume: 62, Issue:2
Pharmacological characterization of MK-6096 - a dual orexin receptor antagonist for insomnia.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (21)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's18 (85.71)24.3611
2020's3 (14.29)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 24.58

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index24.58 (24.57)
Research Supply Index3.26 (2.92)
Research Growth Index4.51 (4.65)
Search Engine Demand Index46.50 (26.88)
Search Engine Supply Index3.90 (0.95)

This Compound (24.58)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials4 (19.05%)5.53%
Reviews6 (28.57%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other11 (52.38%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
acetylene
[no description available]		2.110alkyne;
gas molecular entity;
terminal acetylenic compound
piperidine
[no description available]		2.1110azacycloalkane;
piperidines;
saturated organic heteromonocyclic parent;
secondary amine		base;
catalyst;
human metabolite;
non-polar solvent;
plant metabolite;
protic solvent;
reagent
thiazoles
[no description available]		4.39301,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
pyrimidine
pyrimidine : The parent compound of the pyrimidines; a diazine having the two nitrogens at the 1- and 3-positions.		7.110diazine;
pyrimidines		Daphnia magna metabolite
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		4.97401,2,3-triazole
benzofurans
Benzofurans: Compounds that contain a BENZENE ring fused to a furan ring.		4.3930
sb 408124
SB 408124: a hypocretin receptor type 1 (HcrtR1) antagonist		3.6420organohalogen compound;
quinolines
sb 334867-a
1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea: selective OX1 receptor antagonist		2.2510naphthyridine derivative
jnj 10397049
JNJ 10397049: a selective orexin receptor-2 antagonist		4.3930
sb674042
SB674042: nonpeptide antagonist to the human orexin-1 receptor; structure in first source		3.1810
tcs ox2 29
[no description available]		3.1810
almorexant
almorexant: a dual orexin receptor antagonist for treatment of insomnia		5.3950isoquinolines
suvorexant
suvorexant: an orexin receptor antagonist; structure in first source. suvorexant : An aromatic amide obtained by formal condensation of the carboxy group of 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid with the secondary amino group of 5-chloro-2-[(5R)-5-methyl-1,4-diazepan-1-yl]-1,3-benzoxazole. An orexin receptor antagonist used for the management of insomnia.		6.07701,3-benzoxazoles;
aromatic amide;
diazepine;
organochlorine compound;
triazoles		central nervous system depressant;
orexin receptor antagonist
sb 649868
N-((1-((5-(4-fluorophenyl)-2-methyl-4-thiazolyl)carbonyl)-2-piperidinyl)methyl)-4-benzofurancarboxamide: antagonist of both orexin 1 and orexin 2 receptors; for treating insomnia; structure in first source		5.3950
act-462206
ACT-462206: an antagonist of both orexin 1 and oxexin 2 receptors; structure in first source		4.4530
piperidines
Piperidines: A family of hexahydropyridines.		10.58144
gsk 1059865
[no description available]		3.6420
act-335827
[no description available]		4.1120
ConditionIndicatedRelationship StrengthStudiesTrials
Chronic Insomnia
[description not available]		07.3661
Sleep Initiation and Maintenance Disorders
Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition.		19.3661
Long Sleeper Syndrome
[description not available]		03.0310
Anxiety
Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.		03.0310
Sleep Wake Disorders
Abnormal sleep-wake schedule or pattern associated with the CIRCADIAN RHYTHM which affect the length, timing, and/or rigidity of the sleep-wake cycle relative to the day-night cycle.		03.0310
Gelineau Syndrome
[description not available]		03.0410
Narcolepsy
A condition characterized by recurrent episodes of daytime somnolence and lapses in consciousness (microsomnias) that may be associated with automatic behaviors and AMNESIA. CATAPLEXY; SLEEP PARALYSIS, and hypnagogic HALLUCINATIONS frequently accompany narcolepsy. The pathophysiology of this disorder includes sleep-onset rapid eye movement (REM) sleep, which normally follows stage III or IV sleep. (From Neurology 1998 Feb;50(2 Suppl 1):S2-S7)		03.0410
Congenital Zika Syndrome
[description not available]		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.2510
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510
Asymmetric Diabetic Proximal Motor Neuropathy
[description not available]		04.4811
Diabetic Neuropathies
Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)		16.4811
Depression, Involutional
Form of depression in those MIDDLE AGE with feelings of ANXIETY.		04.4511
Depressive Disorder, Major
Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5)		16.4511
Abdominal Migraine
[description not available]		04.8221
Migraine Disorders
A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)		04.8221