Details
Stereochemistry | ACHIRAL |
Molecular Formula | C12H8O4 |
Molecular Weight | 216.1895 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=C2OC(=O)C=CC2=CC3=C1OC=C3
InChI
InChIKey=QXKHYNVANLEOEG-UHFFFAOYSA-N
InChI=1S/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3
DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/09048slr037_methoxsalen_lbl.pdfCurator's Comment: description was created based on several sources, including:
http://www.drugbank.ca/drugs/DB00553
https://en.wikipedia.org/wiki/Methoxsalen
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/09048slr037_methoxsalen_lbl.pdf
Curator's Comment: description was created based on several sources, including:
http://www.drugbank.ca/drugs/DB00553
https://en.wikipedia.org/wiki/Methoxsalen
Methoxsalen — also called xanthotoxin, marketed under the trade names Oxsoralen, Deltasoralen, Meladinine — is a drug used to treat psoriasis, eczema, vitiligo, and some cutaneous lymphomas in conjunction with exposing the skin to UVA light from lamps or sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. The dosage comes in 10 mg tablets, which are taken in the amount of 30 mg 75 minutes before a PUVA (psoralen + UVA) light treatment. Chemically, methoxsalen belongs to a class of organic natural molecules known as furanocoumarins. They consist of coumarin annulated with furan. It can also be injected and used topically. The exact mechanism of action of methoxsalen with the epidermal melanocytes and keratinocytes is not known. The best known biochemical reaction of methoxsalen is with DNA. Methoxsalen, upon photoactivation, conjugates and forms covalent bonds with DNA which leads to the formation of both monofunctional (addition to a single strand of DNA) and bifunctional adducts (crosslinking of psoralen to both strands of DNA) Reactions with proteins have also been described. Methoxsalen acts as a photosensitizer. Administration of the drug and subsequent exposure to UVA can lead to cell injury. Orally administered methoxsalen reaches the skin via the blood and UVA penetrates well into the skin. If sufficient cell injury occurs in the skin, an inflammatory reaction occurs. The most obvious manifestation of this reaction is delayed erythema, which may not begin for several hours and peaks at 48–72 hours. The inflammation is followed, over several days to weeks, by repair which is manifested by increased melanization of the epidermis and thickening of the stratum corneum. The mechanisms of therapy are not known. In the treatment of vitiligo, it has been suggested that melanocytes in the hair follicle are stimulated to move up the follicle and to repopulate the epidermis. In the treatment of psoriasis, the mechanism is most often assumed to be DNA photodamage and resulting decrease in cell proliferation but other vascular, leukocyte, or cell regulatory mechanisms may also be playing some role. Psoriasis is a hyperproliferative disorder and other agents known to be therapeutic for psoriasis are known to inhibit DNA synthesis. The most commonly reported side effect of methoxsalen alone is nausea, which occurs with approximately 10% of all patients. This effect may be minimized or avoided by instructing the patient to take methoxsalen with milk or food, or to divide the dose into two portions, taken approximately one-half hour apart. Other effects include nervousness, insomnia, and psychological depression.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2311221 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | 8-MOP Approved Usewhen the diagnosis has been supported by biopsy. Photochemotherapy is intended to be administered only in conjunction
with a schedule of controlled doses of long wave ultraviolet radiation. Launch Date1954 |
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Primary | 8-MOP Approved UsePhotochemotherapy (methoxsalen with long wave ultraviolet radiation) is indicated for the repigmentation
of idiopathic vitiligo Launch Date1954 |
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Palliative | 8-MOP Approved Usein the palliative treatment of the skin manifestations of cutaneous T-cell lymphoma (CTCL) in persons who have not been responsive to other forms of treatment. While this dosage form of methoxsalen has been approved for use in combination with photopheresis, Oxsoralen Ultra Capsules have not been approved for that use. Launch Date1954 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
127.63 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33745439/ |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
125.16 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33745439/ |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
155 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6861433/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN serum | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
|
129 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3729509 |
0.6 mg/kg single, oral dose: 0.6 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
335.48 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33745439/ |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
321.25 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33745439/ |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
420 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6861433/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN serum | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
|
521 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3729509 |
0.6 mg/kg single, oral dose: 0.6 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
61 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6861433/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN serum | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
|
2.38 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3729509 |
0.6 mg/kg single, oral dose: 0.6 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
METHOXSALEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
0.6 mg/kg 4 times / week multiple, oral Recommended Dose: 0.6 mg/kg, 4 times / week Route: oral Route: multiple Dose: 0.6 mg/kg, 4 times / week Sources: |
unhealthy, 49.7 |
|
70 mg 4 times / week multiple, oral Recommended Dose: 70 mg, 4 times / week Route: oral Route: multiple Dose: 70 mg, 4 times / week Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Cataract... AEs leading to discontinuation/dose reduction: Cataract Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Cataract | Disc. AE | 70 mg 4 times / week multiple, oral Recommended Dose: 70 mg, 4 times / week Route: oral Route: multiple Dose: 70 mg, 4 times / week Sources: |
unhealthy Health Status: unhealthy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
yes [IC50 2 uM] | ||||
yes [Ki 0.11 uM] | ||||
yes [Ki 0.2 uM] | ||||
yes [Ki 0.8 uM] | ||||
yes [Ki 20 uM] | ||||
yes [Ki 20 uM] | ||||
yes [Ki 25 uM] | ||||
yes [Ki 3 uM] | ||||
yes [Ki 35 uM] | ||||
yes [Ki 75 uM] | ||||
yes | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: (PMDA infomation form) 19 |
yes | |||
Page: (PMDA infomation form) 19 |
yes | |||
Page: (PMDA infomation form) 19 |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Characterization of the mutational specificity of DNA cross-linking mutagens by the Lac+ reversion assay with Escherichia coli. | 2001 |
|
Immunomodulating effects of extracorporeal photochemotherapy in rat experimental allergic encephalomyelitis. | 2001 |
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Phototherapy of psoriasis: comparative experience of different phototherapeutic approaches. | 2001 |
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Expression of CYP6B1 and CYP6B3 cytochrome P450 monooxygenases and furanocoumarin metabolism in different tissues of Papilio polyxenes (Lepidoptera: Papilionidae). | 2001 Apr 27 |
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A comparison of the effect of narrow-band ultraviolet B in the treatment of psoriasis after salt-water baths and after 8-methoxypsoralen baths. | 2001 Aug |
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Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after oral administration. | 2001 Aug |
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Assessment of the phototoxic potential of compounds and finished topical products using a human reconstructed epidermis. | 2001 Fall |
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Livedoid vasculitis responding to PUVA therapy. | 2001 Feb |
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Treatment of stage II cutaneous T-cell lymphoma with interferon alfa-2a and extracorporeal photochemotherapy: a prospective controlled trial. | 2001 Feb |
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The PUVA-turban as a new option of applying a dilute psoralen solution selectively to the scalp of patients with alopecia areata. | 2001 Feb |
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Pharmacokinetic behaviour of sublingually administered 8-methoxypsoralen for PUVA therapy. | 2001 Feb |
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Aquagenic pruritus responding to intermittent photochemotherapy. | 2001 Jan |
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Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. | 2001 Jan |
|
[Heracl'eum mantegazzi'anum: photosensitization]. | 2001 Jan 18 |
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Furanochromone radical cations: generation, characterization and interaction with DNA. | 2001 Jul 2 |
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Induction of apoptosis, depletion of glutathione, and DNA damage by extracorporeal photochemotherapy and psoralen with exposure to UV light in vitro. | 2001 Jul-Aug |
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Extracorporeal photopheresis: a review. | 2001 Jun |
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Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro. | 2001 Jun |
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In vitro inhibition of cytochrome P450 enzymes in human liver microsomes by a potent CYP2A6 inhibitor, trans-2-phenylcyclopropylamine (tranylcypromine), and its nonamine analog, cyclopropylbenzene. | 2001 Mar |
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Synthesis and properties of peptide nucleic acids containing a psoralen unit. | 2001 Mar 22 |
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The psoralens adversely affect reproductive function in male wistar rats. | 2001 Mar-Apr |
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Evaluation of the immunomodulatory mechanisms of photochemotherapy in transplantation. | 2001 May |
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The effect of methoxsalen dose on ultraviolet-A-induced erythema. | 2001 May |
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A bioassay using the human hepatoblastoma cell line HepG2 for detecting phototoxicity of furocoumarins. | 2001 Oct |
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Formation of 6-formyl-7-hydroxy-8-methoxycoumarin and 5,8-dioxopsoralen by reaction of 8-methoxypsoralen with H2O2 and potassium superoxide (KO2) catalyzed by halogenated or perhalogenated 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides. | 2001 Sep |
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Inhibition of itch-scratch response by fruits of Cnidium monnieri in mice. | 2001 Sep |
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Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study. | 2001 Sep |
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A study of the expression of the xenobiotic-metabolising cytochrome P450 proteins and of testosterone metabolism in bovine liver. | 2001 Sep 1 |
|
Mitochondrial alterations in fanconi anemia fibroblasts following ultraviolet A or psoralen photoactivation. | 2002 Feb |
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Effects of the isoflavone 4',5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage. | 2002 Feb |
|
Synthesis and biological evaluation of a new furo[2,3-h]quinolin-2(1H)-one. | 2002 Feb 28 |
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Evaluation of synergism in the feeding deterrence of some furanocoumarins on Spodoptera littoralis. | 2002 Jan |
|
Extracorporeal photopheresis in cutaneous T-cell lymphoma and graft-versus-host disease induces both immediate and progressive apoptotic processes. | 2002 Jan |
|
Reliability of nested polymerase chain reaction in the diagnosis of bacterial endophthalmitis. | 2002 Jan |
|
Cell-impermeant pyridinium derivatives of psoralens as inhibitors of keratinocyte growth. | 2002 Jan 1 |
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Time course of 8-methoxypsoralen concentrations in skin and plasma after topical (bath and cream) and oral administration of 8-methoxypsoralen. | 2002 Mar |
|
Decreased survival of UV-irradiated Staphylococcus aureus in the presence of 8-methoxypsoralen in the post-irradiation plating medium. | 2002 Mar |
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Bullous phytophotodermatitis associated with high natural concentrations of furanocoumarins in limes. | 2002 Mar |
|
Novel angular furo and thieno-quinolinones: synthesis and preliminary photobiological studies. | 2002 Mar |
|
Simultaneous determination of furanocoumarins in infusions and decoctions from "Carapiá" (dorstenia species) by high-performance liquid chromatography. | 2002 Mar 13 |
|
Epoxidation of some natural furocoumarins and furochromones using gamma-ray. | 2002 May-Jun |
|
In vivo effect of 5- and 8-methoxypsoralens and cimetidine on R,S-warfarin metabolism in rat. | 2002 Sep-Oct |
Sample Use Guides
VITILIGO THERAPY : Two capsules (10 mg each) in one dose taken with milk or in food two to four hours before ultraviolet light exposure.
PSORIASIS THERAPY: The methoxsalen capsules should be taken 2 hours before UVA exposure with some food or milk
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3114156
Curator's Comment: 8-Methoxypsoralen was assessed for its effects on in vitro lymphocyte proliferation in the absence of ultraviolet radiation. 8-Methoxypsoralen inhibited both the phytohemagglutinin and concanavalin A-induced proliferation of normal human peripheral blood lymphocytes in a time and dose-dependent manner.
8-Methoxypsoralen inhibited both the phytohemagglutinin and concanavalin A-induced proliferation of normal human peripheral blood lymphocytes in a time and dose-dependent manner.
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000010217
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WHO-ATC |
D05AD02
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D05BA02
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NDF-RT |
N0000007909
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EU-Orphan Drug |
EU/3/06/374
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WHO-VATC |
QD05AD02
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FDA ORPHAN DRUG |
80594
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NCI_THESAURUS |
C1420
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N0000007909
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FDA ORPHAN DRUG |
117298
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NDF-RT |
N0000009801
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C25760
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QD05BA02
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NDF-RT |
N0000175879
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N0000007909
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FDA ORPHAN DRUG |
74293
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LIVERTOX |
620
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NDF-RT |
N0000175984
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30
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m7329
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298-81-7
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2505
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D008730
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1417001
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100000092592
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6854
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PRIMARY | RxNorm | ||
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METHOXSALEN
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U4VJ29L7BQ
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DB00553
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4114
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C643
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CHEMBL416
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DTXSID8020830
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Methoxsalen
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SUB14541MIG
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ACTIVE MOIETY