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Identification
Name Almotriptan
Accession Number DB00918 (APRD00169)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Almogran
Axert
Brand mixtures Not Available
Categories
  • Vasoconstrictor Agents
  • Anti-inflammatory Agents
  • Anti-migraine Agents
  • Selective Serotonin Agonists
  • Serotonin Agonists
CAS number 181183-52-8
Weight Average: 335.464
Monoisotopic: 335.166747749
Chemical Formula C17H25N3O2S
InChI Key InChIKey=WKEMJKQOLOHJLZ-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Tryptamines and Derivatives
Substructures
  • Indoles and Indole Derivatives
  • Pyrroles
  • Sulfonyls
  • Pyrrolidines
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Tryptamines and Derivatives
  • Sulfonamides
Pharmacology
Indication For the treatment of acute migraine headache in adults
Pharmacodynamics Almotriptan 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 action Almotriptan binds with high affinity to human 5-HT1B and 5-HT1D receptors leading to cranial blood vessel constriction.
Absorption Not Available
Volume of distribution
  • 180 to 200 L
Protein binding 35%
Metabolism Not Available
Route of elimination Almotriptan 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 life 3-4 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)]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ortho mcneil janssen pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Axert 12 12.5 mg tablet Box 300.14 USD box
Axert 6 6.25 mg tablet Box 150.05 USD box
Axert 12.5 mg tablet 24.05 USD tablet
Axert 6.25 mg tablet 24.05 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5565447 1995-11-07 2015-11-07
Canada 2120028 1999-03-23 2013-07-19
Properties
State solid
Experimental Properties
Property Value Source
logP 1.6 Not Available
Predicted Properties
Property Value Source
water solubility 1.21e-01 g/l ALOGPS
logP 2.04 ALOGPS
logP 1.52 ChemAxon
logS -3.4 ALOGPS
pKa (strongest acidic) 17.14 ChemAxon
pKa (strongest basic) 9.55 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 56.41 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 94.52 ChemAxon
polarizability 37.01 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 123606 Link_out
PubChem Substance 46505165 Link_out
ChemSpider 110198 Link_out
ChEBI 520985 Link_out
ChEMBL 520985 Link_out
Therapeutic Targets Database DAP001345 Link_out
PharmGKB PA10246 Link_out
Drug Product Database 2248128 Link_out
RxList http://www.rxlist.com/cgi/generic2/almotriptan.htm Link_out
Drugs.com http://www.drugs.com/cdi/almotriptan.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Almotriptan Link_out
ATC Codes
  • N02CC05
AHFS Codes
  • 28:32.28
PDB Entries Not Available
FDA label show (778 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Citalopram Increased risk of CNS adverse effects
Conivaptan CYP3A4 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.
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dihydroergotamine Possible severe and prolonged vasoconstriction
Dihydroergotoxine Possible severe and prolonged vasoconstriction
Ergonovine Possible severe and prolonged vasoconstriction
Ergotamine Possible severe and prolonged vasoconstriction
Escitalopram Increased risk of CNS adverse effects
Fluoxetine Increased risk of CNS adverse effects
Fluvoxamine Increased risk of CNS adverse effects
Isocarboxazid The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, almotriptan. Concomitant therapy is contraindicated.
Itraconazole This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Ketoconazole This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Methylergonovine Possible severe and prolonged vasoconstriction
Methysergide Possible severe and prolonged vasoconstriction
Nefazodone Increased risk of CNS adverse effects
Paroxetine Increased risk of CNS adverse effects
Phenelzine The MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, almotriptan. Concomitant therapy is contraindicated.
Sertraline Increased risk of CNS adverse effects
Sibutramine Increased risk of CNS adverse effects
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine The 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.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole Voriconazole, 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.
Zolmitriptan Concomitant 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 1B receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28222 Link_out
Gene: HTR1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 1D receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28221 Link_out
Gene: HTR1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

UniProt ID: P21397 Link_out
Gene: MAOA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds

UniProt ID: P31513 Link_out
Gene: FMO3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19