IngredientsDimethylpentylamine is the common supplement-label name for a small aliphatic amine that exists in two isomeric forms, distinguished by the position of the methyl group on the heptane carbon chain. 1,3-Dimethylamylamine (1,3-DMAA), also known as 1,3-dimethylpentylamine and methylhexaneamine (MHA), is an aliphatic amine with stimulant properties. 1,4-Dimethylamylamine (1,4-DMAA), also known as 1,4-dimethylpentylamine or as 5-methylhexan-2-amine, is a stimulant drug of the alkylamine family related to methylhexanamine (1,3-DMAA; geranamine).
The two isomers are structurally similar but distinct chemical entities. 1,3-DMAA (also called methylhexanamine or methylhexaneamine) is the far more extensively studied and commercially used form, and is the primary subject of published safety and pharmacology literature. Methylhexanamine, also known as 1,3-dimethylamylamine (1,3-DMAA), is an alkylamine closely structurally related to other alkylamines including 1,3-dimethylbutylamine (1,3-DMBA), 1,4-dimethylamylamine (1,4-DMAA), heptaminol, octodrine, isometheptene, and tuaminoheptane. Methylhexanamine and other related alkylamines are similar in chemical structure to phenethylamines and amphetamines, but lack a closed ring.
The complete list of synonyms and identifiers documented in the scientific and regulatory literature includes:
1,3-DMAA is a stimulatory molecule chemically similar to ephedrine. The structural similarity to amphetamines is pharmacologically meaningful: it is a small molecule that shares structural similarity to amphetamines.
Supplement manufacturers have historically claimed that dimethylpentylamine is a natural extract derived from Pelargonium graveolens, commonly sold as geranium oil or rose geranium extract. 1,3-DMAA is reportedly found naturally only in geranium plants (Pelargonium graveolens). The presence of 1,3-DMAA in geranium plants was first reported in a paper published in the Journal of Guizhou Institute of Technology by Ping et al., who detected the presence of 1,3-DMAA at a concentration of 0.66% in geranium oil isolated from fresh stems and leaves in P. graveolens plant collected from the Rongjang region of Guizhou province in China.
However, the validity of these claims has been extensively disputed. The natural occurrence of DMAA in geranium oil (Pelargonium graveolens) has been controversial as published studies report contradicting findings. It is unclear if the difference in detection of DMAA in Pelargonium species is a result of the loss during extraction methods, different detection capabilities of analytical methods, or if the content of DMAA is dependent on the species and geographical origins.
The presence of 1,3-DMAA in geranium plants was first reported in a paper published in 1996, but some have questioned the identification of 1,3-DMAA in that study. Since then, a number of additional studies have been published, largely reporting the absence of 1,3-DMAA in geranium plants and commercial geranium oils. However, in two recent studies, 1,3-DMAA was detected in geranium plant tissues and a geranium oil sample using a simplified extraction approach on tissues and oil sourced from China.
One peer-reviewed analytical study using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) found evidence in favour of natural occurrence: these results provide strong evidence that 1,3-DMAA and 1,4-DMAA are naturally present in both geranium plant and geranium oil. However, this finding is difficult to reconcile with the levels found in commercial supplements; 1,4-DMAA is found in small amounts in geranium plants. However, some supplements have been found to contain much larger amounts than are found in nature. Because of this, there is a concern that manufacturers are using synthetic 1,4-DMAA that is made in a laboratory rather than obtaining it from a natural source.
The U.S. Food and Drug Administration's position is unequivocal: according to the FDA, there isn't any reliable scientific data to support the claim that DMAA occurs naturally in geranium plants. Both isomers have been identified in dietary supplement products sold commercially. 1,4-DMAA has been identified in dietary supplements. Supplement labels have used the botanical names as a form of concealment: in some products, a herbal ingredient was declared, e.g., Pelargonium graveolens and Dendrobium nobile, without providing any information about the presence of DMAA in order to 'camouflage' and make it difficult to identify the parent active ingredient.
Dimethylpentylamine (specifically 1,3-DMAA) has a documented pharmaceutical history predating its re-emergence in the supplement market. Methylhexanamine is an indirect sympathomimetic drug invented and developed by Eli Lilly and Company and marketed as an inhaled nasal decongestant from 1948 until it was voluntarily withdrawn from the market in the 1980s.
The original trademark for DMAA, since expired, was granted to Eli Lilly and Company in 1971 (US trademark number: 72382454) for Forthane™. DMAA was not in supplements prior to the Dietary Supplement and Health Education Act of 1994 (DSHEA); hence, DMAA would be classified as a New Dietary Ingredient (NDI) by the Food and Drug Administration (FDA). The first recorded use of the Forthane trademark was October 4, 1948, and it was indicated as a vasoconstrictor consisting of methylhexanamine.
Initially developed in 1944 by Eli Lilly as a nasal decongestant, the vasoconstrictive and sympathomimetic efficacy of DMAA has been well characterized. Original reports indicated that DMAA was a less potent and longer-lasting vasoconstrictor compared to epinephrine, with systemic toxicity greater than ephedrine, but less than amphetamine.
The compound is an aliphatic amine; the pharmaceutical industry had a strong interest in compounds in this class as nasal decongestants in the early 20th century, which led to methylhexanamine and four other similar compounds being brought to market for that use: tuaminoheptane, octin (isometheptene), oenethyl (2-methylaminoheptane), and propylhexedrine.
In the original patent application, it was described as having less CNS effects than amphetamine, and less systemic symptoms than ephedrine. Also in comparison with ephedrine, it was deemed more volatile and therefore preferable in applications requiring volatility: nasal sprays, inhalers.
After the trademark expired and the pharmaceutical product was withdrawn, Patrick Arnold reintroduced methylhexanamine in 2006 as a dietary supplement, after the final ban of ephedrine in the United States in 2005. Arnold introduced it under the trademarked name Geranamine, a name held by his company, Proviant Technologies. The use of DMAA within the sport supplement world began in approximately 2006, possibly in relation to the banning of ephedrine in April 2004.
It reappeared in both dietary supplements as a substitute for ephedrine, and in party pills as an alternative to 3,4-methylenedioxymethamphetamine and/or 1-benzylpiperazine, after these substances were banned. Following its introduction to the market, it became one of the most widely used stimulants, and several case reports started to raise concerns about the safety and adverse effects of 1,3-DMAA.
Dimethylamylamine (DMAA), also known as methylhexaneamine, or 1,3-dimethylpentylamine, is a simple aliphatic amine. As a single active compound rather than a botanical extract, there are no complex secondary constituents to characterize — the pharmacological activity resides entirely in the parent amine molecule itself.
Similar to amphetamine, DMAA possesses a methyl substituent on the alpha-carbon which prolongs the drug's half-life by sterically interfering with monoamine oxidase. This substituent also enhances its ability to act as a catecholamine reuptake inhibitor.
The 1,3 and 1,4 isomers are structurally distinct. 1,4-DMAA produces sympathomimetic effects in animals and humans. 1,4-DMAA and other alkylamine stimulants may act as catecholamine releasing agents. Unlike octodrine and methylhexanamine, 1,4-DMAA has never been used as a pharmaceutical drug.
The primary pharmacological mechanism of 1,3-DMAA is sympathomimetic in nature. DMAA appears to provide a sympathomimetic effect in human subjects. It mimics the effects on the sympathetic nervous system of neurotransmitters such as epinephrine, norepinephrine, and dopamine.
At the cellular level, DMAA is best characterized as an indirect-acting sympathomimetic and catecholamine releasing agent. A publication by Alsufyani and Docherty (2019) reported that 1,3-DMAA induced tachycardia and pressor response in rats via an indirect adrenergic action related to stimulated norepinephrine release.
The mechanism at peripheral sympathetic nerve terminals involves catecholamine displacement. The primary location for peripherally-acting releasing agents is in the terminal ends of nerves extending from the sympathetic nervous system to organs such as the heart, kidney, and to nerves supplying the vasculature. In these locations, releasing agents cause a localized release of norepinephrine into the synapse which acts post-synaptically to increase heart rate (beta-1), cause renal vasodilation (beta-1), and peripheral vasoconstriction (alpha-1). To a smaller extent, they are able to stimulate the release of epinephrine (EP) and norepinephrine (NE) from chromaffin cells of the adrenal gland. Since epinephrine is a strong beta-2 receptor agonist, peripheral vasodilation may partly offset the vasoconstriction induced by norepinephrine which acts primarily on alpha-1 receptors.
Importantly, more recent preclinical research has identified the dopamine transporter (DAT) as a molecular target of DMAA. Docking analysis and molecular dynamics simulations revealed that DMAA binds to the S1 substrate binding site and induces a conformational change from outward-facing open to outward-facing closed states, similar to known substrates. Further supporting substrate-like effects of DMAA, the drug stimulated dopamine transporter endocytosis in a heterologous expression system via cocaine- and protein kinase A-sensitive mechanisms, mirroring findings with amphetamine. Together, these data indicate that DMAA elicits neurologic effects by binding to and regulating function of the dopamine transporter.
DMAA also inhibits the norepinephrine transporter (NET): importantly, DMAA inhibits the norepinephrine transporter (NET), another known amphetamine target, with an IC₅₀ of 0.41 µM. Amphetamine can stimulate NET endocytosis, so it is likely that DMAA mediates biologic effects through interactions with the NET as well. As DMAA has a greater preference for NET:DAT than d-amphetamine, it may carry greater risks from pressor actions but lower risks from positive reinforcement, limiting abuse potential.
The mechanism of action for its original nasal decongestant use was vasoconstriction — the blood vessels in the nose would constrict so that less blood flow would lead to less nasal discharge.
Despite these mechanistic insights, it is important to note that there is scant research describing the mechanism of action of DMAA, making it difficult to gauge risks or therapeutic potential.
In its pharmaceutical history, dimethylpentylamine was administered as an inhaled nasal decongestant (inhaler/nasal spray). In the dietary supplement market, it appeared predominantly in the following forms:
Historically, when DMAA was more commonly found in dietary supplements, dosages ranged from 25 mg to 75 mg per serving, depending on the product and its intended use. A 2012 regulatory review noted that 1,3-dimethylamylamine (DMAA) is a pressor amine often found in food supplements for athletes at dosages of 25–65 mg.
The pharmacokinetic study by Schilling et al. (2013), published in BMC Pharmacology and Toxicology, used a single 25 mg oral dose as its test dose. Eight men reported to the lab in the morning following an overnight fast and received a single 25 mg oral dose of DMAA. Blood samples were collected before and through 24 hours post-DMAA ingestion and analyzed for plasma DMAA concentration.
Detailed pharmacokinetic data in humans are limited to a single dedicated investigation. Analysis of seven participants showed DMAA had an oral clearance of 20.02 ± 5 L·hr⁻¹, an oral volume of distribution of 236 ± 38 L, and terminal half-life of 8.45 ± 1.9 hr. Lag time, the delay in appearance of DMAA in the circulation following extravascular administration, varied among participants but averaged approximately 8 minutes (0.14 ± 0.13 hr). The peak DMAA concentration for all subjects was observed within 3–5 hours following ingestion and was very similar across subjects, with a mean of ~70 ng·mL⁻¹.
These findings indicate a consistent pattern of increase across subjects with regards to peak DMAA concentration, with peak values approximately 15–30 times lower than those reported in case studies linking DMAA intake with adverse events. A single 25 mg dose of DMAA does not meaningfully impact resting heart rate, blood pressure, or body temperature.
A notable limitation of this pharmacokinetic study is that it used only a 25 mg dose; a patient in one case report purportedly ingested two "tablets" containing DMAA (later confirmed by analysis to contain 278 mg of DMAA per "capsule": total dosage = 556 mg), along with 150 mg of caffeine and one can of beer.
Like other sympathomimetics, acute use of DMAA appears to promote vasoconstriction, which can lead to a dose-dependent elevation in blood pressure — a finding that has been documented in controlled laboratory studies. However, the picture from controlled trials is more nuanced. 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. In varying concentrations of caffeine and DMAA, there appears to be no effect on heart rate, while DMAA affected blood pressure and the rate-pressure product in a dose-dependent manner. These changes were not related to changes in norepinephrine or epinephrine, and caffeine/DMAA does not appear to be additive.
DMAA mimics the effects on the sympathetic nervous system of neurotransmitters such as epinephrine, norepinephrine, and dopamine. By doing so, it delivers a stimulatory effect, as well as a claimed feeling of euphoria — a response cited in several anecdotal reports. One study investigating a multi-ingredient supplement containing DMAA reported cognitive effects: results indicated that participants had significantly improved reaction time and increased scores on the cognitive-efficiency index following ingestion of the DMAA-containing supplement. However, these results were produced using a multi-ingredient formula, precluding attribution to DMAA alone.
Despite widespread marketing as a performance enhancer, the evidence base is weak. While anecdotal reports of improved exercise performance are common, only one published experiment was designed to investigate the ergogenic properties of 1,3-dimethylamylamine alone or in combination. Ergogenic effects of the combination of caffeine and DMAA substances on running performance have not yet been supported.
Eight weeks of supplementation with a DMAA-containing supplement or placebo did not demonstrate interactions for body weight, body composition, skinfold thickness, serum lipids, or appetite. Heart rate, systolic blood pressure, and rate pressure product were higher for supplement compared to placebo. Ingestion of a DMAA-containing product (OxyELITE Pro™) resulted in an increase in blood markers of lipolysis, as well as metabolic rate, during a two-hour post-ingestion time period. An increase in hemodynamic variables was also observed. These findings are in reference to a sample of healthy men and women who were naïve to treatment with the dietary supplement.
Notable case reports have associated DMAA consumption with cerebral hemorrhaging, myocardial infarction (MI), liver injury, and death. Cerebral hemorrhage occurred in three patients who consumed DMAA. The cases documented by Gee et al. are among the most cited: in these case studies, which cite cerebral hemorrhage following DMAA ingestion, individuals reported ingesting a single dose of DMAA (for its stimulant properties), often in conjunction with caffeine and alcohol.
A preclinical study published in PMC examined the abuse liability of DMAA using animal models. DMAA produced dose-dependent locomotor depression and fully substituted for cocaine and partially substituted for methamphetamine. In the conditioned place-preference assay, DMAA produced an inverted-U-shaped dose-response curve, with intermediate doses producing significant place preference. These animal-model findings are preliminary and cannot be directly extrapolated to humans.
The Whitehead et al. (2013) randomized placebo-controlled trial, published in Nutrition and Metabolic Insights (PMC3698473), represents the longest available controlled human study of DMAA supplementation. Twenty-five 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. Prior work indicated 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. Intervention studies involving both two and eight weeks of treatment with finished products containing 1,3-dimethylamylamine indicated minimal or no change in bloodborne markers of health. No adverse events were noted and the supplement was well-tolerated based on subject self-report. A critical limitation is the small sample size; due to the fact that the sample size is small, additional well-designed experiments of similar scope, inclusive of larger sample sizes, are needed to extend these findings.
Evidence strength: The available controlled human trial data (predominantly from the Bloomer group at the University of Memphis) are limited to small samples of healthy men using commercially available multi-ingredient formulas, with a maximal follow-up of 10 weeks. Confounding by co-ingredients (caffeine, creatine, etc.) cannot be excluded. Evidence is therefore preliminary and insufficient to draw firm conclusions about long-term cardiovascular safety or efficacy. The FDA considers the design of the clinical studies to be lacking; however, the agency notes that the clinical studies still raise safety concerns.
Four studies are available that used the caffeine/DMAA combination in a placebo-controlled design, and the health implications of DMAA in these studies have been unremarkable. Ergogenic effects of the combination of these substances on running performance have not yet been supported.
Evidence strength: The evidence that DMAA improves athletic performance is absent from controlled research. Few human studies have been conducted using DMAA or DMAA-containing supplements. Therefore, scant data exist regarding its precise mechanism(s) of action.
Heart rate, systolic blood pressure, and rate pressure product were higher for supplement compared to placebo. Ingestion of OxyELITE Pro™ resulted in an increase in blood markers of lipolysis, as well as metabolic rate, during a two-hour post-ingestion time period. However, these are acute biomarker findings, and eight weeks of supplementation with the supplement or placebo did not demonstrate interactions for body weight, body composition, skinfold thickness, serum lipids, or appetite.
Evidence strength: Weak. Acute increases in lipolytic biomarkers have not translated into documented changes in body weight or composition over controlled trial periods. No high-quality, adequately powered, long-term randomized clinical trial on weight loss outcomes exists.
The Schilling et al. (2013) study (NCT01765933) represents the first data to characterize the oral pharmacokinetic profile of DMAA. With a single 25 mg dose, findings indicate a consistent pattern of increase across subjects with regards to peak DMAA concentration, with peak values approximately 15–30 times lower than those reported in case studies linking DMAA intake with adverse events. A single 25 mg dose of DMAA does not meaningfully impact resting heart rate, blood pressure, or body temperature.
Evidence strength: This single-dose study in eight men cannot be used to infer the pharmacokinetics of the higher doses (50–75+ mg) typical of supplement use, or the pharmacokinetics in women, the elderly, or those with cardiovascular disease.
Dose-response studies of DMAA were performed with Swiss-Webster mice in locomotor and conditioned place-preference assays. The discriminative stimulus effects of DMAA were investigated in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from saline. DMAA produced dose-dependent locomotor depression and fully substituted for cocaine and partially substituted for methamphetamine. In the conditioned place-preference assay, DMAA produced an inverted-U-shaped dose-response curve, with intermediate doses producing significant place preference.
Evidence strength: Preclinical (animal) only. These findings cannot be directly extrapolated to human abuse potential.
A number of adverse events and at least five deaths have been associated with methylhexanamine-containing supplements. The FDA compiled evidence across multiple channels: after over 100 reports of illness attributed to DMAA, including six deaths, the Food and Drug Administration issued a warning to cease its sale. The agency said it received 42 adverse event reports on products containing DMAA.
There is limited scientific research on the safety of DMAA, but products containing DMAA have been linked to several serious adverse events such as liver injury, cardiac arrest, stroke, brain hemorrhage (bleeding in the brain), and death (following physical exertion).
The most alarming reports involve bleeding in the brain. A published case series documented three adults who suffered cerebral hemorrhages after using DMAA, including subarachnoid hemorrhage, a particularly dangerous type of brain bleed. One reported case involved a person who took two capsules containing 278 mg of DMAA each (a total of 556 mg) along with caffeine and alcohol.
One patient consumed two tablets containing 66 mg DMAA and 84 mg caffeine after consuming alcohol. Another patient, while in a bar, mixed one quarter of a packet of a powdered substance labeled as containing 50 mg DMAA into a drink.
The FDA has stated that methylhexanamine "is known to narrow the blood vessels and arteries, which can elevate blood pressure and may lead to cardiovascular events ranging from shortness of breath and tightening in the chest to heart attack." This substance narrows blood vessels and arteries, which can raise blood pressure, and may lead to cardiovascular problems such as shortness of breath, arrhythmias, tightening in the chest, and heart attack, as well as seizures and other neurological and psychological conditions.
This is particularly important for those who may be hypertensive, those who use other supplements or drugs known to elevate blood pressure, and/or those using DMAA in the context of strenuous resistance exercise, an activity known to have the potential to induce an acute hypertensive response.
There have also been reports of secondary open-angle glaucoma related to methylhexanamine supplementation.
In two publications, Gee et al. reviewed four separate cases in which individuals reported ingesting pure DMAA in conjunction with alcohol in recreational settings. Individuals experienced adverse outcomes, including severe headaches, vomiting, and involuntary twitching. Neurological effects include seizures and psychological disturbances. These risks increase significantly when DMAA is combined with caffeine, which is nearly universal in the supplements that contain it.
A survey of 4,374 U.S. armed forces personnel conducted when DMAA was still legal (2010–2011) found that overall, 11% of survey respondents used dietary supplements labelled as containing DMAA at least once per week. Use of dietary supplements containing 1,3-DMAA was associated with multiple self-reported adverse events, including tachycardia, tremors, dizziness, and numbness/tingling sensations.
The U.S. Department of Defense convened a review panel, which concluded: the existing evidence does not conclusively establish that DMAA-containing substances are causally associated with adverse medical events. However, a consistent theme among the studies is that DMAA use potentially affects cardiovascular function, just as other sympathomimetic stimulants. Widespread use of DMAA-containing products by tens of thousands of Service members — often in combination with other substances — increases the likelihood of observing serious adverse events, even if the overall risk of a DMAA-related event is low. DMAA should be further studied to evaluate its safety.
DMAA possesses a methyl substituent on the alpha-carbon which prolongs the drug's half-life by sterically interfering with monoamine oxidase. This structural property has implications for interactions with monoamine oxidase inhibitors (MAOIs), as simultaneous use could theoretically lead to excessive sympathomimetic stimulation, though direct human pharmacokinetic interaction studies have not been published.
In 2012, the FDA issued warning letters to manufacturers and distributors calling for cessation of DMAA sales and use within dietary supplement formulations, partly because required safety data supporting DMAA's use was lacking. Supplements containing DMAA were considered "adulterated." Adverse event reports following DMAA ingestion prompted the FDA's actions.
The FDA has also warned that DMAA is not a dietary ingredient and thus is not Dietary Supplement Health and Education Act (DSHEA) compliant. Over the past several years, the FDA has used different methods to ensure DMAA-containing products are taken off the market. These actions are being taken to protect consumers and get these products off the shelves as quickly as possible. Starting in 2012, the FDA has issued warning letters to companies notifying them that marketing DMAA-containing products violates the law.
At the international level: DMAA is banned for use in sports by the World Anti-Doping Agency (WADA). It is listed on WADA's Prohibited List, which means that athletes who test positive for DMAA in doping controls can face sanctions. In 2010, DMAA was placed in the Prohibited List of doping agents from the group of S6 — Stimulants. The Therapeutic Goods Administration (TGA) of Australia has listed DMAA as a Schedule 10 substance under the Poisons Standard.
Despite regulatory actions, as of 2019, the stimulant remains available in sports and weight loss supplements in the US. No studies conducted in laboratory animals supporting the safe use of 1,3-DMAA as an ingredient in food were identified in the FDA's updated review.
For 1,4-DMAA specifically, the US Food and Drug Administration (FDA) states that supplements containing 1,4-DMAA appear to be illegal and recommends that these products not be taken. 1,4-DMAA is also included in the World Anti-Doping Agency's prohibited substances list.
Surveys of commercially available supplements have confirmed that prohibited stimulants continue to appear in products. Two-thirds of supplements analyzed in one study contained compounds that were not listed on the product's label.
The body of evidence for dimethylpentylamine (1,3-DMAA and 1,4-DMAA) is notably sparse, low-powered, and largely confined to short-duration trials in healthy young men using multi-ingredient proprietary formulas. From a scientific point of view, there exist very few studies focused on the safety of DMAA. Those that have been conducted have failed to note any significant adverse effects with regular DMAA ingestion, other than an acute rise in blood pressure with use. At the same time, the volume of well-controlled, long-term safety studies involving DMAA is scant and based on this, some believe that DMAA should not be allowed for use in dietary supplements. Multiple adverse event reports have been filed which cite the involvement of DMAA. These events may be linked to the well-described pressor actions of DMAA and the resulting dose-dependent rise in blood pressure with use.
No area of use — including athletic performance enhancement, weight loss, cognitive improvement, or ADHD — is supported by sufficient, high-quality human clinical evidence to establish efficacy. The mechanistic and preclinical evidence is more developed, particularly regarding sympathomimetic activity and dopamine/norepinephrine transporter interactions, but these findings have not been translated into controlled human outcome studies.
Health conditions that Dimethylpentylamine may help support.
Body systems that Dimethylpentylamine may help support.
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