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Identification
NameAlmotriptan
Accession NumberDB00918  (APRD00169)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Almotriptan is a triptan drug for the treatment of migraine headaches. Almotriptan is in a class of medications called selective serotonin receptor agonists. It works by narrowing blood vessels in the brain, stopping pain signals from being sent to the brain, and stopping the release of certain natural substances that cause pain, nausea, and other symptoms of migraine. Almotriptan does not prevent migraine attacks.

Structure
Thumb
Synonyms
SynonymLanguageCode
1-(((3-(2-(Dimethylamino)ethyl)indol-5-yl)methyl)sulfonyl)pyrrolidineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AlmogranNot Available
AxertNot Available
Brand mixturesNot Available
Categories
CAS number181183-52-8
WeightAverage: 335.464
Monoisotopic: 335.166747749
Chemical FormulaC17H25N3O2S
InChI KeyWKEMJKQOLOHJLZ-UHFFFAOYSA-N
InChI
InChI=1S/C17H25N3O2S/c1-19(2)10-7-15-12-18-17-6-5-14(11-16(15)17)13-23(21,22)20-8-3-4-9-20/h5-6,11-12,18H,3-4,7-10,13H2,1-2H3
IUPAC Name
dimethyl(2-{5-[(pyrrolidine-1-sulfonyl)methyl]-1H-indol-3-yl}ethyl)amine
SMILES
CN(C)CCC1=CNC2=C1C=C(CS(=O)(=O)N1CCCC1)C=C2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIndoles and Derivatives
SubclassTryptamines and Derivatives
Direct parentTryptamines and Derivatives
Alternative parentsIndoles; Benzene and Substituted Derivatives; Substituted Pyrroles; Sulfonamides; Pyrrolidines; Sulfonyls; Tertiary Amines; Polyamines
Substituentsindole; substituted pyrrole; benzene; sulfonyl; sulfonamide; pyrrole; sulfonic acid derivative; pyrrolidine; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the tryptamines and derivatives. These are compounds containing the tryptamine backbone, which is structurally characterized by an indole ring subsituted at the thrid position by an ethanamine.
Pharmacology
IndicationFor the treatment of acute migraine headache in adults
PharmacodynamicsAlmotriptan is a selective 5-hydroxytryptamine receptor subtype agonist indicated for the acute treatment of migraine attacks with or without aura in adults. Almotriptan is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Almotriptan is an agonist for a vascular 5-hydroxytryptamine receptor subtype (probably a member of the 5-HT1D family) having only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Almotriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Almotriptan in humans.
Mechanism of actionAlmotriptan binds with high affinity to human 5-HT1B and 5-HT1D receptors leading to cranial blood vessel constriction.
AbsorptionNot Available
Volume of distribution
  • 180 to 200 L
Protein binding35%
Metabolism
SubstrateEnzymesProduct
Almotriptan
N-desmethylalmotriptanDetails
Almotriptan
2-{5-[(pyrrolidine-1-sulfonyl)methyl]-1H-indol-3-yl}acetic acidDetails
Almotriptan
2-{5-[(pyrrolidine-1-sulfonyl)methyl]-1H-indol-3-yl}ethan-1-olDetails
Almotriptan
1-[({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}methane)sulfonyl]pyrrolidin-2-olDetails
Route of eliminationAlmotriptan is eliminated primarily by renal excretion (about 75% of the oral dose), with approximately 40% of an administered dose excreted unchanged in urine. Approximately 13% of the administered dose is excreted via feces, both unchanged and metabolized.
Half life3-4 hours
Clearance
  • 57 L/h [healthy]
  • 34.2 L/h [moderate renal impairment (creatinine clearance between 31 and 71 mL/min)]
  • 9.8 L/h [severe renal impairment (creatinine clearance between 10 and 30 mL/min)]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
Gene symbol: GNB3
UniProt: P16520
rs5443 Not AvailableT AlleleBetter response to drug treatment17361120
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9781
Caco-2 permeable - 0.7421
P-glycoprotein substrate Substrate 0.5636
P-glycoprotein inhibitor I Non-inhibitor 0.8282
P-glycoprotein inhibitor II Non-inhibitor 0.8679
Renal organic cation transporter Non-inhibitor 0.553
CYP450 2C9 substrate Non-substrate 0.7898
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.6292
CYP450 1A2 substrate Non-inhibitor 0.605
CYP450 2C9 substrate Non-inhibitor 0.8089
CYP450 2D6 substrate Non-inhibitor 0.6273
CYP450 2C19 substrate Non-inhibitor 0.8581
CYP450 3A4 substrate Non-inhibitor 0.8929
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8486
Ames test Non AMES toxic 0.6532
Carcinogenicity Non-carcinogens 0.8588
Biodegradation Not ready biodegradable 0.9508
Rat acute toxicity 2.5976 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.5255
hERG inhibition (predictor II) Non-inhibitor 0.6008
Pharmacoeconomics
Manufacturers
  • Ortho mcneil janssen pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Axert 12 12.5 mg tablet Box300.14USDbox
Axert 6 6.25 mg tablet Box150.05USDbox
Axert 12.5 mg tablet24.05USDtablet
Axert 6.25 mg tablet24.05USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States55654471995-11-072015-11-07
Canada21200281999-03-232013-07-19
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.121ALOGPS
logP2.04ALOGPS
logP1.52ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)17.14ChemAxon
pKa (Strongest Basic)9.55ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area56.41 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity94.52 m3·mol-1ChemAxon
Polarizability37.01 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Ramasubramanian Sridharan, Vandanapu Purushotham, Kori Algooram, Nitin Pradhan, “Crystalline forms of almotriptan and processes for their preparation.” U.S. Patent US20070112055, issued May 17, 2007.

US20070112055
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound123606
PubChem Substance46505165
ChemSpider110198
ChEBI520985
ChEMBLCHEMBL1505
Therapeutic Targets DatabaseDAP001345
PharmGKBPA10246
Drug Product Database2248128
RxListhttp://www.rxlist.com/cgi/generic2/almotriptan.htm
Drugs.comhttp://www.drugs.com/cdi/almotriptan.html
WikipediaAlmotriptan
ATC CodesN02CC05
AHFS Codes
  • 28:32.28
PDB EntriesNot Available
FDA labelshow(778 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
CitalopramIncreased risk of CNS adverse effects
ConivaptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Use an initial almotriptan dose of 6.25mg when using almotriptan with a strong CYP3A4 inhibitor, and do not exceed 12.5mg of almotriptan in any 24-hour period. Avoid concurrent use of almotriptan with a strong CYP3A4 inhibitor in patients with impaired hepatic or renal function.
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DihydroergotaminePossible severe and prolonged vasoconstriction
ErgonovinePossible severe and prolonged vasoconstriction
ErgotaminePossible severe and prolonged vasoconstriction
EscitalopramIncreased risk of CNS adverse effects
FluoxetineIncreased risk of CNS adverse effects
FluvoxamineIncreased risk of CNS adverse effects
IsocarboxazidThe MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, almotriptan. Concomitant therapy is contraindicated.
ItraconazoleThis potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
KetoconazoleThis potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
MethylergometrinePossible severe and prolonged vasoconstriction
MethysergidePossible severe and prolonged vasoconstriction
NefazodoneIncreased risk of CNS adverse effects
ParoxetineIncreased risk of CNS adverse effects
PhenelzineThe MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, almotriptan. Concomitant therapy is contraindicated.
SertralineIncreased risk of CNS adverse effects
SibutramineIncreased risk of CNS adverse effects
TramadolIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TranylcypromineThe MAO inhibitor, Tranylcypromine, may reduce the metabolism and clearance of the serotonin 5-HT1D receptor agonist, Almotriptan. Risk of serotonin syndrome and Almotriptan toxicity. Concomitant therapy should be avoided.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrimipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of almotriptan by decreasing its metabolism. The initial and maximum doses should not exceed 6.25 mg and 12.5 mg, respectively during concomitant therapy. Concomitant therapy should be avoided in patients with impaired hepatic or renal function.
ZolmitriptanConcomitant use of two serotonin 5-HT1D receptor agonists, such as zolmitriptan and almotriptan, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.
Food Interactions
  • Take without regard to meals.
  • The absorption is unaffected by food.

Targets

1. 5-hydroxytryptamine receptor 1B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1B P28222 Details

References:

  1. Napier C, Stewart M, Melrose H, Hopkins B, McHarg A, Wallis R: Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors. Eur J Pharmacol. 1999 Mar 5;368(2-3):259-68. Pubmed
  2. Fleishaker JC, Sisson TA, Carel BJ, Azie NE: Pharmacokinetic interaction between verapamil and almotriptan in healthy volunteers. Clin Pharmacol Ther. 2000 May;67(5):498-503. Pubmed
  3. van den Broek RW, MaassenVanDenBrink A, de Vries R, Bogers AJ, Stegmann AP, Avezaat CJ, Saxena PR: Pharmacological analysis of contractile effects of eletriptan and sumatriptan on human isolated blood vessels. Eur J Pharmacol. 2000 Oct 27;407(1-2):165-73. Pubmed
  4. Knyihar-Csillik E, Tajti J, Csillik AE, Chadaide Z, Mihaly A, Vecsei L: Effects of eletriptan on the peptidergic innervation of the cerebral dura mater and trigeminal ganglion, and on the expression of c-fos and c-jun in the trigeminal complex of the rat in an experimental migraine model. Eur J Neurosci. 2000 Nov;12(11):3991-4002. Pubmed
  5. Bou J, Domenech T, Puig J, Heredia A, Gras J, Fernandez-Forner D, Beleta J, Palacios JM: Pharmacological characterization of almotriptan: an indolic 5-HT receptor agonist for the treatment of migraine. Eur J Pharmacol. 2000 Dec 20;410(1):33-41. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. 5-hydroxytryptamine receptor 1D

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1D P28221 Details

References:

  1. Napier C, Stewart M, Melrose H, Hopkins B, McHarg A, Wallis R: Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors. Eur J Pharmacol. 1999 Mar 5;368(2-3):259-68. Pubmed
  2. Bou J, Domenech T, Puig J, Heredia A, Gras J, Fernandez-Forner D, Beleta J, Palacios JM: Pharmacological characterization of almotriptan: an indolic 5-HT receptor agonist for the treatment of migraine. Eur J Pharmacol. 2000 Dec 20;410(1):33-41. Pubmed
  3. Gras J, Llupia J, Llenas J, Palacios JM: Safety profile of almotriptan, a new antimigraine agent. Effects on central nervous system, renal function and respiratory dynamics. Arzneimittelforschung. 2001 Sep;51(9):726-32. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Amine oxidase [flavin-containing] A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] A P21397 Details

References:

  1. McEnroe JD, Fleishaker JC: Clinical pharmacokinetics of almotriptan, a serotonin 5-HT receptor agonist for the treatment of migraine. Clin Pharmacokinet. 2005;44(3):237-46. Pubmed
  2. Gras J, Llenas J, Jansat JM, Jauregui J, Cabarrocas X, Palacios JM: Almotriptan, a new anti-migraine agent: a review. CNS Drug Rev. 2002 Fall;8(3):217-34. Pubmed
  3. Salva M, Jansat JM, Martinez-Tobed A, Palacios JM: Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan. Drug Metab Dispos. 2003 Apr;31(4):404-11. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Salva M, Jansat JM, Martinez-Tobed A, Palacios JM: Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan. Drug Metab Dispos. 2003 Apr;31(4):404-11. Pubmed
  3. McEnroe JD, Fleishaker JC: Clinical pharmacokinetics of almotriptan, a serotonin 5-HT receptor agonist for the treatment of migraine. Clin Pharmacokinet. 2005;44(3):237-46. Pubmed

3. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. McEnroe JD, Fleishaker JC: Clinical pharmacokinetics of almotriptan, a serotonin 5-HT receptor agonist for the treatment of migraine. Clin Pharmacokinet. 2005;44(3):237-46. Pubmed

4. Dimethylaniline monooxygenase [N-oxide-forming] 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Dimethylaniline monooxygenase [N-oxide-forming] 3 P31513 Details

References:

  1. Salva M, Jansat JM, Martinez-Tobed A, Palacios JM: Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan. Drug Metab Dispos. 2003 Apr;31(4):404-11. Pubmed

5. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Salva M, Jansat JM, Martinez-Tobed A, Palacios JM: Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan. Drug Metab Dispos. 2003 Apr;31(4):404-11. Pubmed

6. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Salva M, Jansat JM, Martinez-Tobed A, Palacios JM: Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan. Drug Metab Dispos. 2003 Apr;31(4):404-11. Pubmed

7. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Salva M, Jansat JM, Martinez-Tobed A, Palacios JM: Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan. Drug Metab Dispos. 2003 Apr;31(4):404-11. Pubmed

8. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Salva M, Jansat JM, Martinez-Tobed A, Palacios JM: Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan. Drug Metab Dispos. 2003 Apr;31(4):404-11. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 20, 2013 12:39