Effects of monotherapy with a monoamine oxidase B inhibitor on motor symptoms in Parkinson’s disease are dependent on frontal function

Murakami, Hidetomo; Okumura, Motohiro; Ozawa, Masakazu; Mimori, Masahiro; Maku, Takahiro; Shiraishi, Tomotaka; Kitagawa, Tomomichi; Takatsu, Hiroki; Sato, Takeo; Komatsu, Teppei; Sakai, Kenichiro; Umehara, Tadashi; Omoto, Shusaku; Mitsumura, Hidetaka; Iguchi, Yasuyuki

doi:10.1007/s10072-022-06499-6

Cited by 3 publications

(1 citation statement)

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“…MAO-B inhibitors are of therapeutic value in Parkinson's disease since they may prevent central dopamine degradation. Irreversible (e.g., selegiline and rasagiline) and reversible (e.g., safinamide) inhibitors of MAO-B are established therapy in Parkinson's disease and although providing only moderate symptomatic benefit, these agents are used as monotherapy or in combination with levodopa in late-stage Parkinson's disease while having few pharmacological adverse effects and safety concerns (Alborghetti et al, 2024;Murakami et al, 2023). MAO-mediated metabolism is also a prominent source of hydrogen peroxide production in the central nervous system, which may be converted to highly reactive hydroxyl free radicals if not detoxified (Pizzinat et al, 1999;Edmondson, 2014).…”

Section: Introductionmentioning

confidence: 99%

Investigation of Novel Thiazole Derivatives Bearing the Benzenesulfonamide Moiety as MAO Inhibitors with a Promising Activity Profiles

Shetnev,

Efimova,

Olga

et al. 2023

Preprint

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We have recently reported that a series of 1,3,4-oxadiazol-2-ylbenzenesulfonamides acts as potent and specific monoamine oxidase B (MAO-B) inhibitors with some compounds possessing potencies in the nanomolar range. While sulfonamide compounds (e.g., zonisamide) have been reported to inhibit the MAO enzymes, nanomolar MAO inhibition potencies for this class are not frequently observed. The present study expanded on these findings by replacing the 1,3,4-oxazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized by reaction of an α-haloketone with a substituted carbothioamide. The results of the MAO inhibition studies showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of human MAO-B. The most potent MAO-B inhibitor exhibited an in vitro IC50 value of 0.103 µM (3j). The derivatives were, however, weaker inhibitors of human MAO-A with the most potent compound exhibiting an IC50 value of 11.9 µM (3a). Examination of the structure-activity relationships (SARs) showed that the most potent MAO-B inhibition was obtained with substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concludes that 1,3-thiazolylbenzenesulfonamides represent a class of potent and specific MAO-B inhibitors, which may serve as leads for the development of new treatments for disease states such as Parkinson’s disease.

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Section: Introductionmentioning

confidence: 99%