生物活性

• 描述Methoxsalen is a potent tricyclic furocoumarin suicide inhibitor of CYP (cytochrome P-450), is an agent used to treat psoriasis, eczema, vitiligo and some cutaneous Lymphomas in conjunction with exposing the skin to sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. Methoxsalen pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (15mg/kg, po) for periods up to 6- and 24-hr postnicotine administration, respectively^[3]. Using the guinea pig as an experimental model, UV-A (long-wave UV) irradiation given immediately after the topical application of methoxsalen resulted in the notable suppression of tritiated thymidine incorporation into epidermal basal cells^[4]. Oral methoxsalen when used in the higher dose followed by sun exposure is an effective treatment for psoriasis^[5]. Administration of methoxsalen (50 mumol X kg-1 i.p.) increased 4-fold the hexobarbital sleeping time in rats. Methoxsalen (25-1000 microM) decreased cytochrome P-450 in vitro, in the presence of EDTA; this effect required NADPH and oxygen, was decreased by piperonyl butoxide and was increased by phenobarbital pretreatment. Similarly, administration of methoxsalen (125 mumol X kg-1 i.p.) decreased cytochrome P-450 and monooxygenase activities in vivo; the decrease in cytochrome P-450 was enhanced by phenobarbital pretreatment and was prevented by piperonyl butoxide^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00045305	-	-	Completed	-	-
  NCT00724061	Lymphoma	Not Applicable	Terminated(Closed early due to... more >> poor accrual.) Collapse <<	-	United States, Illinois ... more >> Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois, United States, 60611-3013 Collapse <<
  NCT00045305	Leukemia Myel... more >>odysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Collapse <<	Phase 2	Completed	-	United States, Arizona ... more >> Mayo Clinic Scottsdale Scottsdale, Arizona, United States, 85259-5499 United States, Florida Mayo Clinic - Jacksonville Jacksonville, Florida, United States, 32224 United States, Massachusetts Tufts-NEMC Cancer Center Boston, Massachusetts, United States, 02111 United States, Minnesota Mayo Clinic Cancer Center Rochester, Minnesota, United States, 55905 United States, Ohio Jewish Hospital Cancer Center Cincinnati, Ohio, United States, 45236 United States, Pennsylvania Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104-4283 Collapse <<

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• 参考文献

• [1] Zhang W, Kilicarslan T, et al. Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro. Drug Metab Dispos. 2001 Jun;29(6):897-902.

  [2] Maenpaa J, Juvonen R, et al Metabolic interactions of methoxsalen and coumarin in humans and mice. Biochem Pharmacol. 1994 Oct 7;48(7):1363-9.

  [3] Alsharari SD, Siu EC, Tyndale RF, Damaj MI. Pharmacokinetic and pharmacodynamics studies of nicotine after oral administration in mice: effects of methoxsalen, a CYP2A5/6 inhibitor. Nicotine Tob Res. 2014 Jan;16(1):18-25

  [4] Danno K, Toda K, Ishida H, Horio T. Topical methoxsalen followed immediately by long-wave UV irradiation. A preliminary report on the treatment of psoriasis. Arch Dermatol. 1982 Jul;118(7):471-3

  [5] Parrish JA, White AD, Kingsbury T, Zahar M, Fitzpatrick TB. Photochemotherapy of psoriasis using methoxsalen and sunlight. A controlled study. Arch Dermatol. 1977 Nov;113(11):1529-32

  [6] Fouin-Fortunet H, Tinel M, Descatoire V, Letteron P, Larrey D, Geneve J, Pessayre D. Inactivation of cytochrome P-450 by the drug methoxsalen. J Pharmacol Exp Ther. 1986 Jan;236(1):237-47

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