Pantothenic acid antagonists

Adverse effects, sometimes fatal, have been reported in patients taking calcium hopantenate, notably encephalopathy with metabolic acidosis and semicoma (1) and a Reye-like syndrome (2) this may be due to pantothenic acid deficiency, as hopantenate is a pantothenic acid antagonist. In elderly people, liver dysfunction and gastrointestinal upsets have been reported (3,4). In Japan, where the product was introduced in 1978, the control authorities in 1988 issued a series of warnings with respect to problems caused by hopantenate (5). 

Noda S, Umezaki H, Yamamoto K, Araki T, Murakami T, Ishii N. Reye-hke syndrome following treatment with the pantothenic acid antagonist, calcium hopantenate. J Neurol Neurosurg Psychiatry 1988 51(4) 582-5. 

Calcium hopantenate. The administration of the pantothenic acid antagonist, calcium hopantenate (also called calcium homopantothenate), can decrease CoA and inhibit mitochondrial p-oxidation, and it has caused several cases of Reye s-like syndrome in Japan (Noda et al. 1988). 

Pantoyltaurine is one of many pantothenic acid antagonists which block competitively the utilization of the vitamin by microorganisms. Shive has discussed many antagonistic analogues in a thorough manner . One of the most widely used antagonists is w-methylpantothenic acid which has been used to induce pantothenic acid deficiencies in animals and human beings . 

Pantothenic acid 10-15 mg/day. Deficiency causes apathy, depression, impaired adrenal function, and muscular weakness, co -Methylpantothenic acid is a specific antagonist. The calcium salt, calcium pantothenate, is the usual commercial form. 

Antagonists of folic acid include aminoplerin (4-aniino-ptcroylglulamic acidj. methotrexate tamethopterin), pyrimethamine, and 4-ammo-picroylas-partic acid. Synergists include biotin, pantothenic acid, niacin, vitamins B. Bo Bf, B 2. C, and E. somatotrophin (growth hormone), and testosterone. 

Antagonists of niacin include pyridine-3-sulfonie acid (in bacteria), 3-acetylpyridine, 6-aminonicctinamide, and 5-thiazole carboxamide. Synergists include vitamins Bj, B, B. B]). and D, pantothenic acid, folic acid, and soiualotrupliin (growth hormone). 

Antagonists of thiamine include pyrithiamine, oxythiamine, and 2-n-butyl homologue. Synergists include vitamins B2. Bg, Bi2. and niacin, pantothenic acid, and somatotrophin (growth hormone). 

There are some well-described deficiency syndromes, the well-established therapeutic use of vitamin K antagonists as oral anticoagulants and the well-known positive effects of pantothenic acid on skin hydration/moisturization and wound healing, which apparently lacks scientific solid base. Apart from that there are not many studies available on the treatment of dermatological disorders with these vitamins, either systemically or topically. Even less is known about transdermal penetration, stability, and formulation dependencies of possible topical applications. 

It should be noted that deficiency states for some vitamins (e.g., pantothenic acid) are practically unknown in human beings. In such cases, deficiency states may be simulated by feeding the subject an appropriate vitamin antagonist. In another series of situations, vitamin deficiencies can be brought about by interfering with their absorption intentionally or may be the result of a disease process. Thus, fat-soluble vitamin deficiency may develop in cases of fat malabsorption syndromes (steatorrhea) sprue, pancreatic insufficiency, and bile duct obstruction. 

Deficiency is well documented in chickens, which develop a pantothenic acid-responsive dermatitis. Other experimental animals show a variety of abnormalities from pantothenic acid deficiency. In human beings dietary deficiency has not been reliably documented, although it has been implicated in the burning foot syndrome (nutritional melalgia). Subjects maintained on pantothenic acid-deficient diets or given the antagonist [Pg.345]

Pantothenic acid is widely distributed in foods, and because it is absorbed throughout the small intestine, it is likely that intestinal bacterial synthesis also makes a contribution to pantothenic acid nutrition. As a result, deficiency has not been unequivocaUyreportedinhumanbeings except in specific depletion studies, which have also frequently used the antagonist < -methyl pantothenic acid. 

Pantothenic acid and its derivatives have essentially no pliarmacological actions per se. Because of the ubiquitous nature of the vitamin, deficiency stales usually do not develop. They have been produced by u.se of synthetic diets devoid of the vitamin or by use of a vitamin antagonist. [Pg.888]

The widespread availability of pantothenic acid in food is commensurate with its many roles and makes an uncomplicated dietary deficiency of pantothenate unlikely in humans. Symptoms have been produced in a few volunteers who have received co-methylpantothenic acid as an antagonist and in people fed semisynthetic diets virtually free of pantothenate. Subjects became irascible and developed postural hypotension and rapid heart rate on exertion, epigastric distress with anorexia and constipation, numbness and tingling of the hands and feet, hyperactive deep tendon... 

Sodium 2,2-dichloropropionate (dalapon, Dowpon ) is much used for killing grass in dicotyledonous crops such as beet and lucerne. Competitive studies in bacteria E. coli) point to its being an antagonist for the incorporation ofpantoic acid [i.e. the left-hand side of 9.38)] into pantothenic acid. This is the main site of its action on grasses its effect is diminished by external pantothenic acid Hilton et al., 1959). 

However, with prolonged maintenance on diets deficient in pantothenic acid and/or administration of its antagonists, it is possible to produce an extensive... 

Pantothenic acid can be accompanied by its biologically active higher homologue known as homopantothenic acid (5-71), which contains 4-aminobutanoic acid (y-aminobutyric acid) instead of P-alanine and acts as an antagonist of pantothenic acid. 

It is known that homopantothenic acid improves the metabohsm of glucose in the brain and the higher functions of the brain and it has been used in Japan to enhance mental functions, especially in Alzheimer s disease. A rare side-effect is an abnormal brain function resulting from the failure of the liver to eliminate toxins (hepatic encephalopathy). This condition was reversed by pantothenic acid supplementation, suggesting that it was due to pantothenic acid deficiency caused by the antagonist homopantothenic acid. 

In early studies on the mode of action of PSII-inhibiting herbicides such as substituted phenylureas and s-triazines, it was observed that the phytotoxic symptoms of these herbicides could be alleviated by the exogenous addition of sugars.Similarly, purine derivatives, such as adenine or guanine, and pantothenic acid have been reported as compensation-type antagonists of the activity of the herbicides amitrole and dalapon, respectively. 

Antagonists of biotin include desthiobiotin in some forms, ureylene phenyl, homobiotin, urelenecyclohexyl butync and valeric acid, norbiotin, avidin, lysolecithin. and biotin sulfone. Synergists indude vitamins B>. B6, B 2, folic acid, pantothenic add. somatotrophin (growth hormone), and testosterone. 

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