Pyridoxine antagonist

Mechanism of Action Acts as a coenzyme for various metabolic functions, including metabolism of proteins, carbohydrates, and fats. Aids in the breakdown of glycogen and in the synthesis of gamma-aminobutyric acid in the CNS. Therapeutic Effect Prevents pyridoxine deficiency. Increases the excretion of certain drugs, such as iso-niazid, that are pyridoxine antagonists. 

Pyridoxine is a component of several enzyme systems involved in N metabolism. In general, diets provide an adequate amount, in the free form or combined with phosphate. Some feedstuffs such as linseed and certain varieties of beans may contain pyridoxine antagonists. Pyridoxine is one of the vitamins that suffers during feed processing, 70-90% of the content in wheat being lost during milling (Nesheim, 1974). A severe deficiency results... 

The administration of the pyridoxine antagonist, deoxypyridoxine, to man (G9) and rats (P6) has been shown to produce a severe disturbance of tryptophan metabolism in these species as manifested by the excretion of large amounts of xanthurenic acid following the administration of a tryptophan load. 

INHIBITION OF HISTIDINE DECARBOXYLATION ttt ffWO The in vivo production of histamine, and of other amines, in rats can be diminished by the use of pyridoxine-deficient diets, pyridoxine antagonists, or non-specific inhibitors such as semicarbazide > i >i . In female rats receiving a pyridoxine-deficient, histamine-free diet, the urinary output of histamine was reduced to about 50% of normal simultaneous administration of semicarbazide further reduced the histamine output to about 20% of normal. However, the histamine content of the tissues of these animals did not differ significantly from those of controls, except in the stomach where the histamine content dropped to a few per cent of normal. 

C10H17N3O5, Mr 259.26, amorphous powder, [ajp + 6.4° (H2O). A y-glutamyl compound from linseed (Linum usitatissimum). The toxic hydrazine derivative acts as a pyridoxine antagonist. ... 

Selective inhibition of serine hydroxymethyl transferase in mice liver and spleen by pyridoxine antagonists, p. 445 in Chemistry and Biology of Pteridines, K. Iwai, M. Akino, M. Goto, Y. Iwanami, eds.,International Academic Printing Co., Tokyo (1970). 

Over 250 analogues of the B vitamers have been reported (11,100). Nearly all have low vitamin B activity and some show antagonism. Among these are the 4-deshydroxy analogue, pyridoxine 4-ethers, and 4-amino-5-hydroxymeth5i-2-methyipyrimidine, a biosynthetic precursor to thiamine. StmcturaHy unrelated antagonists include dmgs such as isoniazid, cycloserine, and penicillamine, which are known to bind to pyridoxal enzyme active sites (4). 

Pyridoxine (10 to 25 mg one to four times daily) is recommended as first-line therapy. If symptoms persist, addition of a histamine-1 receptor antagonist, such as dimenhydrinate, diphenhydramine, or meclizine, is recommended. 

Peripheral neuritis, mental confusion, impairs the optimal utilization of pyridoxine [INH (anti TB drug) is a recognised antagonist]. 

Several Hi antagonist drugs have been studied for possible use in treating "morning sickness." The piperazine derivatives were withdrawn from such use when it was demonstrated that they have teratogenic effects in rodents. Doxylamine, an ethanolamine Hi antagonist, was promoted for this application as a component of Bendectin, a prescription medication that also contained pyridoxine. Possible teratogenic effects of doxylamine were widely publicized in the lay press after 1978 as a... 

Flaxseed or flaxseed meal contains a number of ANFs for livestock, the main ones being linamarin and linatine. Linamarin is a cyanoglycoside, which has the potential to cause cyanide poisoning by the action of the enzyme lina-marase (linase). The mature seed contains little or no linamarin, and linana-marase is normally destroyed by heat during oil extraction. Linatine is a dipeptide that can act as an antagonist for pyridoxine. 

Vitamin deficiency can result from treatment with certain drags. Thus, destruction of intestinal microorganisms by antibiotic therapy can produce symptoms of vitamin K deficiency. Isoniazid, used to treat tuberculosis, is a competitive inhibitor of pyridoxal kinase, which is needed to produce pyridoxal phosphate. Isoniazid can produce symptoms of pyridoxine deficiency. To prevent this, pyridoxine is often incorporated into isoniazid tablets. Methotrexate and related folate antagonists act by competitively inhibiting dihydrofolate reductase (Chapter 27). 

The secretion of prolactin (PRL) is controlled by both stimulatory and inhibitory factors of hypothalamic origin. The inhibitory control is exerted primarily by dopamine, which is released from the tuberoinfundibular dopaminergic (TIDA) neurons into the pituitary portal circulation. Evidence based on peripheral administration of serotonin precursors, agonists or antagonists, intraventricular injection of serotonin, and electrical stimulation of the raphe nucleus indicates that central serotonergic projections to the hypothalamus are involved in the stimulation of PRL. Administration of pyridoxine to deficient rats resulted in a significant increase in plasma PRL (14). 

A compound with similar structure to pyridoxine but which is antagonistic (opposes or neutralizes) to the action of pyridoxine. 

Tuberculosis. The drug isoniazid (isonicotinic acid hydrazide, INH), which is used as a chemotherapeutic agent in treating tuberculosis, has been shown to be an antagonist to pyridoxine, causing a side effect of neuritis in some patients. Treatment with large doses (50 to 100 mg daily) of pyridoxine prevents this effect. 

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