U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Status:
US Previously Marketed
Source:
Phenylcinchoninic Acid U.S.P.
(1921)
Source URL:
First marketed in 1908
Source:
Atophan
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)


Conditions:

Cinchophen, phenylcinchoninic acid, seems to have been discovered in 1887 by Doebner and Gieseke and to have been introduced into medicine under the trade name of atophan in 1908 by Nicolaier and Dohrn. Since that time it has been used extensively for gout as well as for other forms of arthritis and for the relief of pain of all types. Use of Cinchophen in humans ceased in the 1930s due to the discovery that it can cause serious liver damage.
Sesamin is a naturally occurring compound found in sesame oil and in the bark and fruit of certain plant species. SESAMIN, (±)- is a racemic dl-form. The dl-form is also known as fagarol, and may be isolated from the bark of various fagara species. Sesamin, either as the d-form or the dl-form, has now been found to possess psychotropic activity, i.e., administration of appropriate dosages to a human or animal subject elicits a psychotropic response. Sesamin is catered to be a nutritional supplement that confers antioxidant and antiinflammatory effects (if touting its health properties) or possibly being an estrogen receptor modulator and fat burner (if targeting athletes or persons wishing to lose weight). Sesamin has a few mechanisms, and when looking at it holistically it can be summed up as a fatty acid metabolism modifier. It appears to inhibit an enzyme known as delta-5-desaturase (Δ5-desaturase) which is a rate-limiting enzyme in fatty acid metabolism; inhibiting this enzyme results in lower levels of both eicosapentaenoic acid (EPA, one of the two fish oil fatty acids) as well as arachidonic acid, and this mechanism appears to be relevant following oral ingestion. The other main mechanism is inhibiting a process known as Tocopherol-ω-hydroxylation, which is the rate-limiting step in the metabolism of Vitamin E; by inhibiting this enzyme, sesamin causes a relative increase of vitamin E in the body but particularly those of the gamma subset (γ-tocopherol and γ-tocotrienol) and this mechanism has also been confirmed to be active following oral ingestion. Sesamin is a potent and specific inhibitor of delta 5 desaturases in polyunsaturated fatty acid biosynthesis. Sesamin inhibits particular CYP3A enzymes that are involved in vitamin E metabolism, where the enzyme initially ω-hydroxylates vitamin E (required step) and then the rest of vitamin E is subject to fat oxidation. By inhibiting this step, sesamin causes an increase in circulating and organ concentrations of vitamin E. Sesamin is thought to have PPARα activating potential in the liver, but it is uncertain how much practical relevance this has in humans due to this being a mechanism that differs between species.