Absorption, Distribution and Excretion
THE METABOLISM OF (14)C-LABELED FUSARIC ACID WAS STUDIED IN MALE & PREGNANT RATS AFTER ORAL ADMIN OF 20 MG/KG. THE MAJOR PART OF RADIOACTIVITY RETAINED IN THE BODY OF MALE RATS WAS IN THE KIDNEY, LIVER, & PLASMA 30 MIN AFTER ADMIN, & DECLINED RAPIDLY THEREAFTER. MOST (92.9%) OF THE DOSE APPEARED IN URINE BY 24 HR AFTER ADMIN & 93.1% BY 48 HR. A CONSIDERABLE AMOUNT OF RADIOACTIVITY APPEARED IN BILE WITHIN 1 HR AFTER ADMIN. AN EASY TRANSFER OF RADIOACTIVITY INTO THE FETUS WAS SHOWN BY RADIOAUTOGRAPHY OF PREGNANT RATS. THE ACTIVITY WAS NOT DETECTED IN THE FETUS IN 24 HR.

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Metabolism / Metabolites
ZINC, COBALT, & MOLYBDENUM ENHANCE THE BIOSYNTHESIS OF FUSARIC ACID BY FUSARIUM OXYSPORUM. NICOTINIC ACID WAS SLIGHTLY STIMULATORY, & TRYPTOPHAN, CYSTEINE, & THE COMBINATION OF INDOLEACETATE & SERINE MARKEDLY STIMULATED THE SYNTHESIS.
INDOLEACETIC ACID ALONE INHIBITED FUSARIC ACID FORMATION BY FUSARIUM OXYSPORUM, BUT INDOLEACETATE WITH SERINE HAD A STIMULATORY EFFECT. THE COMBINATION OF INDOLEACETATE & SERINE WITH TRYPTOPHAN INHIBITED THE BIOSYNTHESIS. HOMOSERINE SHOWED STIMULATORY ACTIVITY INDEPENDENT OF THE OTHER COMPOUNDS TESTED SINCE IT WAS NOT AFFECTED BY THEIR PRESENCE.
THE BIOSYNTHETIC PATHWAY FOR FUSARIC ACID WAS INVESTIGATED USING 1-(13)C-LABELED & 2-(13)C-LABELED ASPARTATE. CARBON ATOMS 2, 3, 4, & 7 WERE DERIVED FROM ACETATE VIA ASPARTATE OR A RELATED C4 DICARBOXYLIC ACID, WHEREAS CARBONS 5, 6, 8, 9, 10, & 11 WERE DERIVED MORE DIRECTLY FROM ACETATE. ASPARTIC ACID APPARENTLY IS METABOLIZED TO FUSARIC ACID VIA OXALOACETATE, & L-ASPARTATE SERVES AS A DONOR OF NITROGEN, IN AN AMINOTRANSFERASE REACTION, TO A SEPARATE OXALACETATE POOL OF PRIMARILY ENDOGENOUS ORIGIN.
IN RATS, THE MAJOR METABOLITE OF 5-(N-BUTYL)PICOLINAMIDE IS FUSARIC ACID, WHICH IS A DOPAMINE-BETA-HYDROXYLASE INHIBITOR. HENCE, ADMIN OF THE DRUG LOWERS THE CONCN OF ENDOGENOUS L-NORADRENALINE IN THE BRAIN, HEART, & SPLEEN.

Toxicity Summary
Fusaric acid affects neurotransmitter levels by acting as a partial inhibitor on tyrosine-hydroxylase and an inhibitor on dopamine-beta-hydroxylase. This has been shown to cause elevated serotonin, 5-hydroxyindoleacetic acid, tyrosine, and dopamine levels in the brain, as well as decreased norepinephrine levels. These changes in neurotransmitter levels may be responsible for effects such as hypotension, altered behavior and locomotive activity, neurological disorders, and developmental problems. (A3020, A3021, A3022, A3023)

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Interactions
WHEN FUSARIC ACID (100 MG/KG, IP) WAS ADMIN TO MALE MICE 6 HR AFTER ALCOHOL WITHDRAWAL, BRAIN NORADRENALINE, DOPAMINE, & SEROTONIN CONCN WERE 112.8, 186.4, & 652.8 NG/G 4 HR LATER. FUSARIC ACID ADMIN DECREASED BRAIN NORADRENALINE LEVEL ACCOMPANIED BY AN ENHANCED ALCOHOL WITHDRAWAL SYNDROME.

Fusaric acid is a member of pyridines and an aromatic carboxylic acid.
Fusaric acid has been reported in Fusarium fujikuroi, Fusarium verticillioides, and Fusarium solani with data available.
Fusaric acid is a mycotoxin found in various Fusarium species such as Fusarium moniliforme. It has been proposed for a various therapeutic applications but is primarily used as a research tool. Fusaric acid is moderately toxic and can be found in contaminated corn and cereal grains including barley, wheat, millets and sorghum. (L1963, A3020)
A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits DOPAMINE BETA-HYDROXYLASE, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis.

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Mechanism of Action
FUSARIC ACID SUPPRESSED RAPID EYE MOVEMENT (REM) SLEEP IN CATS BUT HAD NO SIGNIFICANT EFFECT ON SLOW WAVE SLEEP. REM SLEEP USUALLY REBOUNDED AFTER A PERIOD OF DRUG-INDUCED SUPPRESSION, INDICATING THAT, ALTHOUGH FUSARIC ACID SUPPRESSED THE PERIPHERAL MANIFESTATIONS OF REM, THE BIOLOGICAL NEED FOR REM WAS NOT ALTERED.
FUSARIC ACID INHIBITED NORADRENALINE & DOPAMINE UPTAKE IN SYNAPTOSOMES FROM RAT HYPOTHALAMUS & CORPUS STRIATUM. THE BASAL OVERFLOW OF NORADRENALINE & DOPAMINE FROM BRAIN STEM & CORPUS STRIATUM SLICES WAS STIMULATED BY FUSARIC ACID. THE DATA SHOW THAT FUSARIC ACID, A DOPAMINE-BETA-HYDROXYLASE INHIBITOR, ALSO EXERTS MARKED EFFECTS IN THE CNS BY INTERFERING WITH OTHER SYNAPTOSOMAL FUNCTIONS.
FUSARIC ACID (100 MG/KG, IP) INCREASED THE LEVELS OF TRYPTOPHAN, SEROTONIN, & 5-HYDROXYINDOLEACETIC ACID IN RAT BRAIN & THE LEVEL OF FREE TRYPTOPHAN IN THE BLOOD INDICATING THAT IN ADDITION TO ITS CNS EFFECT, FUSARIC ACID EXERTS A PERIPHERAL ACTION ON SEROTONIN METABOLISM BY INHIBITING TRYPTOPHAN BINDING TO SERUM ALBUMIN.
FUSARIC ACID (75 MG/KG, IP), AN INHIBITOR OF DOPAMINE BETA-HYDROXYLASE, EFFECTIVE IN THE RELIEF OF TREMORS, RIGIDITY, & SPEECH DIFFICULTIES ASSOCIATED WITH PARKINSONS DISEASE, INCREASED THE BRAIN SEROTONIN LEVELS & DECREASED THE BRAIN NORADRENALINE LEVELS OF RATS.
FUSARIC ACID (FA) INCREASED MONOSYNAPTIC REFLEX NEURAL ACTIVITY IN A DOSE-DEPENDENT MANNER IN CATS. FA DID NOT INCREASE THE BLOOD PRESSURE BUT INHIBITED THE SYNTHESIS OF NOREPINEPHRINE FROM DOPAMINE.

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Therapeutic Uses
Dopamine Agents; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors
EXPTL USE: FUSARIC ACID (100 MG/KG, IP) GIVEN 1.5 HR PRIOR TO WATER-IMMERSION STRESS ALMOST COMPLETELY PREVENTED GASTRIC ULCER FORMATION IN RATS. FUSARIC ACID PROBABLY PREVENTS GASTRIC ULCERATION BY DECREASING NORADRENALINE RELEASE IN THE CNS.

C10H13NO2

179.22

179.095

536-69-6

3442

White to off-white solid powder

1.113g/cm3

329.2ºC at 760mmHg

96-100 °C

152.9ºC

2.122

1

3

4

13

170

0

DGMPVYSXXIOGJY-UHFFFAOYSA-N

InChI=1S/C10H13NO2/c1-2-3-4-8-5-6-9(10(12)13)11-7-8/h5-7H,2-4H2,1H3,(H,12,13)

5-butylpyridine-2-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 62.5 mg/mL (348.73 mM)
H2O: 50 mg/mL (278.99 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (11.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (11.61 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (11.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)