Minoxidil Sulfation in the Hair Follicle

Baker, Carolyn A.; Uno, Hideo; Johnson, George

doi:10.1159/000211315

Cited by 33 publications

(19 citation statements)

References 11 publications

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“…For the antihypertensive and hypertrichotic drug minoxidil, bioactivation by sulfation is beneficial, since the sulfate ester is the pharmacologically active species (74). Elegant experiments demonstrated that the ST responsible for this reaction is expressed in the hair follicles, providing in situ activation of topically applied minoxidil (75), which has found clinical application in the treatment of baldness.…”

Section: Biologically Active and Toxic Sulfatesmentioning

confidence: 99%

Genetic and environmental factors associated with variation of human xenobiotic glucuronidation and sulfation.

Burchell

Coughtrie

1997

Environ Health Perspect

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Glucuronidation and sulfation are phase 2 metabolic reactions catalyzed by large families of different isoenzymes in man. The textbook view that glucuronidation and sulfation lead to the production of harmless conjugates for simple excretion is not valid. Biologically active and toxic sulfates and glucuronides are produced and lead to adverse drug reactions, including immune hypersensitivity. Considerable variation in xenobiotic conjugation is observed as a result of altered expression of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (STs). Recent cloning and expression of human cDNA encoding UGTs and STs has facilitated characterization of isoform substrate specificity, which has been further validated using specific antibodies and human tissue fractions. The availability of cloned/expressed human enzymes and specific antibodies has enabled the investigation of xenobiotic induction and metabolic disruption leading to adverse responses. Genetic polymorphisms of glucuronidation and sulfation are known to exist although the characterization and assessment of the importance of these variations are hampered by appropriate ethical studies in man with suitable safe model compounds. Genetic analysis has allowed molecular identification of defects in well-known hyperbilirubinemias. However, full characterization of the specific functional roles of human UGTs and STs requires rigorous kinetic and molecular analyses of the role of each enzyme in vivo through the use of specific antibodies and inhibitors. This will lead to the better prediction of variation of xenobiotic glucuronidation and sulfation in man. Environ Health Perspect 1 05(Suppl 4): 739-747 (1997)

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Section: Biologically Active and Toxic Sulfatesmentioning

confidence: 99%

Genetic and environmental factors associated with variation of human xenobiotic glucuronidation and sulfation.

Burchell

Coughtrie

1997

Environ Health Perspect

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“…Another possibility is that, analogous to other N-oxides such as minoxidil (Hamamoto and Mori, 1989;Johnson et al, 1992;Baker et al, 1994), the N-oxide of lamotrigine could be a substrate for sulfotransferases leading to a N-sulfate, which might have sufficient chemical reactivity to bind to protein (Fig. 2).…”

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confidence: 99%

Possible Bioactivation Pathways of Lamotrigine

Lu¹,

Uetrecht²

2007

Drug Metab Dispos

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ABSTRACT:The anticonvulsant lamotrigine is associated with idiosyncratic drug reactions, especially skin rashes. Most idiosyncratic reactions are believed to be caused by reactive metabolites. Previous studies have found evidence that an arene oxide is formed in rats; however, when we incubated radiolabeled lamotrigine with rat liver microsomes virtually no covalent binding was detected, and the expected downstream phenolic metabolites are not observed in humans. Rare cases of agranulocytosis have been associated with lamotrigine therapy, and we found that lamotrigine is oxidized to two different N-chloro products by HOCl. The more reactive Nchloro metabolite forms an adduct with N-acetylhistidine, and covalent binding was observed when radiolabeled lamotrigine was incubated with myeloperoxidase/H 2 O 2 /Cl ؊ . Another lamotrigine metabolite is an N-oxide. If this N-oxide were sulfated, it might be sufficiently reactive to bind to protein. The synthetic N-sulfate reacted with N-acetylserine; however, no covalent binding was detected when the radiolabeled N-oxide was incubated with sulfotransferase. We also investigated the possibility that lamotrigine might be oxidized to a free radical by other peroxidases or oxidized by other enzymes such as prostaglandin H synthase or tyrosinase, but no evidence of oxidation was found, and lamotrigine did not cause any detectable increase in lipid peroxidation in vivo. In view of the virtual lack of covalent binding to hepatic microsomes and the lack of any other likely pathway leading to metabolic activation in the skin, it is possible that the parent drug rather than a reactive metabolite causes lamotrigine-induced skin rashes.

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“…Превращение минок-сидила в миноксидил сульфат катализируется фер-ментами сульфотрансферазами. Миноксидил-суль-фотрансферазная активность была обнаружена в гомогенатах печени крыс, человека, тромбоцитах, в фолликулах вибрисс мышей и крыс, в их эпидер-мальных кератиноцитах и эпителиальном влагали-ще корня волоса, в ВФ -в скальпе короткохвостых макак [12,[14][15][16][17][18][19][20].…”

Section: как это работает?unclassified

“…При этом для четырех сульфотрансфераз экспрессия мРНК была обнару-жена в эпидермальных кератиноцитах человека [21]. Во внешней оболочке корня ВФ превращение ми-ноксидила в активную форму миноксидила сульфа-та происходит при помощи эндогенных сульфо-трансферазных ферментов [22][23][24]. Интересные наблюдения были сделаны A. Buhl и соавт.…”

Section: как это работает?unclassified

Minoxidil: a final judgment or a hope?

Gadzhigoroeva¹

2016

Klin. dermatol. venerol.

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ооо «Институт Красивых волос», Москва, Россия, 105082Миноксидил является базовым препаратом для наружной терапии андрогенетической алопеции у мужчин и женщин. Между тем отношение к миноксидилу неоднозначно как среди пациентов, так и среди врачей. недостаточное понимание этиологии разных форм потери волос, отсутствие ясности в механизмах интеракции миноксидила с клетками-мишенями, в особенности с клетками волосяного фолликула, а также специфичность реакции самих волос на ранних этапах лечения компрометирует действие препарата на волосы и организм человека в целом, ограничивая терапевтические возможности при лечении облысения, снижает комплаентность лечению у пациента. в статье приводится обзор научных исследований о стимулирующих механизмах миноксидила на рост волос, о клинической эффективности и преимуществе использования лекарственной формы препарата в виде пены при андрогенетической алопеции.Ключевые слова: миноксидил, пена миноксидил, андрогенетическая алопеция, лечение. Minoxidil: a final judgment or a hope?A.g. gADzHIgoRoEvA «Institute of nice Hair», Moscow, Russia, 105082Minoxidil is a basic drug for the topical treatment of androgenetic alopecia in males and females. Meanwhile, the attitude of both patients and medical professionals to minoxidil is controversial. Insufficient understanding of the etiology of various forms of hair loss, lack of clear understanding of the mechanisms of interaction between minoxidil and target cells, particularly the hair follicle cells, as well as specific reactions of the hair itself at the early stages of treatment, compromise drug effect on the hair and the entire human body, which results in limited therapeutic potential in treatment of hair loss and reduces patients' compliance. This article provides an overview of the research of stimulatory mechanisms of minoxidil on hair growth, clinical efficacy and benefits of the use of foam-like dosage form of the drug in patients with androgenetic alopecia.

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Minoxidil Sulfation in the Hair Follicle

Cited by 33 publications

References 11 publications

Genetic and environmental factors associated with variation of human xenobiotic glucuronidation and sulfation.

Genetic and environmental factors associated with variation of human xenobiotic glucuronidation and sulfation.

Possible Bioactivation Pathways of Lamotrigine

Minoxidil: a final judgment or a hope?

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