4-メチル-2-ヘキサンアミン

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a structure estimation method(2), indicates that 1,3-dimethylamylamine is expected to have moderate mobility in soil(SRC). The pKa of 1,3-dimethylamylamine is estimated to be 10.6(SRC) based on analogy to similar amines(3), indicating that this compound will exist primarily in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of 1,3-dimethylamylamine from moist soil surfaces may occur(SRC) given an estimated Henry's Law constant of 4.2X10-5 atm-cu m/mole(SRC), using a fragment constant estimation method(2). 1,3-Dimethylamylamine is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Environmental biodegradation data specific to 1,3-dimethylamylamine were not available(SRC, 2014). However, similar aliphatic amines (such as amylamine and sec-butylamine) have been classified as readily biodegradable using the Japanese MITI test where these aliphatic amines, present at 100 mg/L, reached 75-94% of theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L(5).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a structure estimation method(2), indicates that 1,3-dimethylamylamine may have moderate adsorption to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4.2X10-5 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 1.1 and 11.1 days, respectively(SRC). According to a classification scheme(4), an estimated BCF of 12(SRC), from an estimated log Kow of 2.16(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. 1,3-Dimethylamylamine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Environmental biodegradation data specific to 1,3-dimethylamylamine were not available(SRC, 2014). However, similar aliphatic amines (such as amylamine and sec-butylamine) have been classified as readily biodegradable using the Japanese MITI test where these aliphatic amines, present at 100 mg/L, reached 75-94% of theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L(5).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,3-dimethylamylamine, which has an estimated vapor pressure of 8.9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 1,3-dimethylamylamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be about 8 hours(SRC), calculated from its rate constant of 4.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). 1,3-Dimethylamylamine does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Twenty commercial volatile oils, three authenticated volatile oils and geranium (Pelargonium graveolens) leaves, stems and oils were analyzed for the presence of 1,3-dimethylamylamine based on marketing of dietary supplements allegedly containing the compound as a constituent of the geranium plant(1); none of the authenticated geranium oils or plant materials contained 1,3-dimethylamylamine at detectable levels (limit of detection: 10 ppb)(1). In contrast, 1,3-dimethylamylamine concentrations 13.6-356 ng/g were detected in geranium plants (Pelargonium graveolens) collected in China in June 2011 and in essential geranium oils from China at concentrations of 167-13271 ng/g(2). Other studies also failed to detect 1,3-dimethylamylamine in geranium plants or geranium oil(3-9).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 1,3-dimethylamylamine can be estimated to be 200(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1,3-dimethylamylamine is expected to have moderate mobility in soil. The pKa of 1,3-dimethylamylamine is estimated to be 10.6 based on analogy to similar amines(SRC,3), indicating that this compound will exist primarily in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ Caffeine and 1,3-dimethylamylamine (DMAA) are widely used alone and in combination with dietary supplements. No investigation has determined the safety profile of chronic intake of caffeine or DMAA, alone or in combination, within the same study design. A total of 50 young and healthy men completed 12 weeks of daily supplementation with either a placebo (n = 11), caffeine at 250 mg/day (n = 14), DMAA at 50 mg/day (n = 13), or caffeine at 250 mg/day + DMAA at 50 mg/day (n = 12). Before and after 6 and 12 weeks of supplementation, the following variables were measured: body mass/composition, resting respiratory rate, blood pressure, 12-lead electrocardiogram, urinalysis, complete blood count, metabolic panel, lipid panel, and oxidative stress, inflammatory, and cardiac biomarkers. No interaction effects were noted for any variable (p > 0.05), with little change occurring across time for subjects in any of the four conditions. With the exception of urinary pH (p = 0.05; Pre (6.5 +/- 0.1) higher than week 6 (6.1 +/- 0.1)) and blood CO2 (p = 0.02; week 12 (25.9 +/- 0.3 mmol/L) higher than week 6 (24.8 +/- 0.3 mmol/L)), no time effect was noted for any other variable (p > 0.05). These data indicate that 12 weeks of daily supplementation with caffeine and DMAA, alone or in combination, does not result in a statistically significant change in any of the measured outcome variables.

/HUMAN EXPOSURE STUDIES/ 1,3-dimethylamylamine is a commonly used ingredient within dietary supplements. Our prior work with this agent indicates a transient increase in blood pressure (systolic in particular) following oral ingestion of a single dosage, but no significant increase in resting blood pressure following chronic ingestion. Moreover, intervention studies involving both two and eight weeks of treatment with finished products containing 1,3-dimethylamylamine indicate minimal or no change in bloodborne markers of health. The present study sought to extend these findings by using a 10-week intervention trial to determine the change in selected markers of health in a sample of men. Methods: 25 healthy men were randomly assigned to either a placebo (n = 13) or to a supplement containing 1,3-dimethylamylamine (n = 12) for a period of 10 weeks. Before and after the intervention, resting blood pressure and heart rate were measured, and blood samples were collected for determination of complete blood count, metabolic panel, and lipid panel. Results: No significant differences were noted between conditions for blood pressure (P > 0.05), although systolic blood pressure increased approximately 6 mmHg with the supplement (diastolic blood pressure decreased approximately 4 mmHg). A main effect for time was noted for heart rate (P = 0.016), with values decreasing from pre to post intervention. There were significant main effects for time for creatinine (increased from pre to post intervention; P = 0.043) and alkaline phosphatase (decreased from pre to post intervention; P = 0.009), with no condition differences noted (P > 0.05). There was a significant interaction noted for low density lipoprotein cholesterol (LDL-C) (P = 0.043), with values decreasing in the supplement group from pre to post intervention approximately 7 mg/ dL (P = 0.034). No other effects of significance were noted for bloodborne variables. Conclusion: These data indicate that a dietary supplement containing 1,3-dimethylamylamine does not result in a statistically significant increase in resting heart rate or blood pressure (although systolic blood pressure is increased approx. 6 mmHg with supplement use). The supplement does not negatively impact bloodborne markers of health. Further study is needed involving a longer intervention period, a larger sample size, and additional measures of health and safety.

1,3-Dimethylamylamine's production and use as an illegal ingredient in dietary supplements(1) may result in its release to the environment through various waste streams(SRC). Although 1,3-dimethylamylamine was approved as a drug for nasal decongestion, no medical use of the compound is recognized today. In 2012, the US FDA issued warning letters to companies notifying them products with 1,3-dimethylamylamine need to be taken off the market(1).

Environmental biodegradation data specific to 1,3-dimethylamylamine were not available(SRC, 2014). However, similar aliphatic amines (such as amylamine and sec-butylamine) have been classified as readily biodegradable using the Japanese MITI test where these aliphatic amines, present at 100 mg/L, reached 75-94% of theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L(1).

An estimated BCF of 12 was calculated in fish for 1,3-dimethylamylamine(SRC), using an estimated log Kow of 2.16(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for 1,3-dimethylamylamine is estimated as 4.2X10-5 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 1,3-dimethylamylamine is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 1.1 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 11.1 days(SRC). 1,3-Dimethylamylamine's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 1,3-Dimethylamylamine is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.9 mm Hg(SRC), determined from a fragment constant method(1).

/LABORATORY ANIMALS: Acute Exposure/ The pressor activity of 39 aliphatic amines was evaluated in dogs. Dogs were pithed, and the amines were injected as sulfate salts into the femoral veins. Doses ranging from 5 to 100 milligrams were tested. Pressor activity was compared with that of epinephrine (51434), and only with reference to the intensity of action. The results were analyzed with reference to chemical structures. When the amino group (NH2) was attached to the second carbon atom of n-alkanes, it invariably became a stronger product than when NH2 was attached to the terminal carbon atom. In the pentane series, substitution of a methyl group at carbon 4 was better than at carbon 3. Methylation of carbon 4 increased the pressor activity when NH2 was on carbon 2. A second methyl group decreased the activity. Ethylation of carbon 5 had less effect than methylation at the same position when NH2 was on carbon 2. In the 2-aminooctane (693163) series, neither methylation at carbon 4 nor hydroxylation at carbon 3 increased pressor activity. Introduction of a methyl group at carbon 6 made 3-aminoheptane (28292424) entirely inactive. The presence of a double bond decreased activity. The most active amine tested was 2-amino-4-methylhexane (105419), followed by 2-aminoheptane (123820); both had seven carbon atoms. The authors conclude that NH2 on carbon 2 has the most favorable influence on pressor activity. The optimal chain length for pressor activity is seven carbons.

/OTHER TOXICITY INFORMATION/ Recent industry-sponsored toxicology studies estimate the maximum tolerated dose in rabbits and rats to be between 125 and 300 mg/kg body weight.

The rate constant for the vapor-phase reaction of 1,3-dimethylamylamine with photochemically-produced hydroxyl radicals has been estimated as 4.9X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 8 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 1,3-Dimethylamylamine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). 1,3-Dimethylamylamine does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Occupational exposure to 1,3-dimethylamylamine may occur through inhalation and dermal contact with this compound at workplaces where 1,3-dimethylamylamine is produced or used. The general population may be exposed to 1,3-dimethylamylamine via ingestion of dietary supplements containing the compound(SRC); however, dietary supplements containing 1,3-dimethylamylamine are illegal and US FDA is doing everything within its authority to remove these products from the market, but 1,3-dimethylamylamine does exist illegally in some supplements(1).

DMAA (1,3-dimethylamylamine) is an amphetamine derivative that has been widely used in sports supplements sold in the United States. Also known as methylhexanamine or geranium extract, DMAA is often touted as a "natural" stimulant, with many claimed functional uses including a body-building aid, an athletic performance enhancer, and a weight-loss aid. Although DMAA at one time was approved as a drug for nasal decongestion, no medical use of DMAA is recognized today. FDA is not aware of any reliable science indicating that DMAA exists naturally in plants.

THERAPEUTIC CATEGORY: Adrenergic

/Former Use/ MEDICATION

Spirodex

Arson Fat Burner Capsule

MethylHex4,2

Code Red

For more Formulations/Preparations (Complete) data for 1,3-Dimethylamylamine (17 total), please visit the HSDB record page.

DMAA, also known as 1,3-dimethylamylamine, methylhexanamine or geranium extract, is an ingredient found illegally in some dietary supplements ... Dietary supplements containing DMAA are illegal and FDA is doing everything within its authority to remove these products from the market. In 2012, FDA issued warning letters to companies notifying them products with DMAA need to be taken off the market or reformulated to remove this substance. Most companies warned are no longer distributing products with DMAA ... DMAA (1,3-dimethylamylamine) is an amphetamine derivative that has been widely used in sports supplements sold in the United States ... often touted as a "natural" stimulant, with many claimed functional uses including a body-building aid, an athletic performance enhancer, and a weight-loss aid. Although DMAA at one time was approved as a drug for nasal decongestion, no medical use of DMAA is recognized today.

Patented as a nasal decongestant and as a topical treatment for hypertrophied or hyperplastic oral tissues.

1,3-Dimethylamylamine or methylexaneamine (DMAA) is a synthetic pharmaceutical patented in the 1940s as a nasal decongestant which can be used as a recreational stimulant. Alleged to occur in nature, DMAA has become a widely used ingredient in sports food supplements, despite its status as a doping agent and concerns over its safety. There is now some doubt as to whether it can be sourced naturally or whether it actually occurs naturally at all. The presence of DMAA was investigated by high performance liquid chromatography (HPLC) in extracts of the leaves and stems of four geranium species and of three well-known cultivars. The amounts of DMAA in commercial geranium (Pelargonium graveolens) oil and the leading sports supplement which uses the ingredient were also measured. DMAA was not found in any of the leaves or stems or in the commercial geranium oil included in this study. Approximately 30 mg per daily dose was found in the food supplement. Therefore, the amount of DMAA found in the supplement is most unlikely to have been /found/ in nature, and it must be concluded that synthetic DMAA, known to be capable of causing severe adverse physiological effects, has been added.