DMHA (dimethylhexylamine)

Dimethylhexylamine (DMHA)

1. Identity: Names, Chemistry, and Forms

Octodrine, also known as dimethylhexylamine (DMHA) and sold under the brand name Vaporpac among others, is a sympathomimetic and stimulant medication that was formerly used in the treatment of hypotension (low blood pressure). Octodrine is the generic name of the drug and its International Nonproprietary Name (INN) and United States Adopted Name (USAN). It is also known by its former developmental code name SKF-51.

Octodrine is a psychoactive central nervous system stimulant. It is an amphipathic primary amine known under many names, including dimethylhexylamine (DMHA) and 2-amino-6-methylheptane. Although the name 2-aminoisoheptane appears on the labels of commercial products, it is ambiguous and may refer to either the 1,4- or 1,5-dimethyl isomer. Commercially, the 1,5-DMHA isomer is most often cited.

The compound carries a large number of synonyms in the scientific and regulatory literature. DMHA is a stimulant ingredient that goes by many names. Those mentioned in FDA warning letters include 2-aminoisoheptane, 1,5-DMHA, 2-amino-6-methylheptane, 1,5-Dimethylhexylamine, 2-Isooctyl amine, and Octodrine. Additional regulatory synonyms documented by the Banned Substances Control Group include 6-amino-2-methylheptane, 6-methyl-2-heptanamine, α,ε-dimethylhexylamine, Amidrine, Isoctaminum, Vaporpac, and Aconitum kusnezoffii / aconite extract.

Octodrine is a synthetic stimulant in the alkylamine family. Chemically, it is a primary amine related to other sympathomimetic stimulants that act on the central nervous system and cardiovascular system. Its structure presents some similarities with that of other stimulants including AMP Citrate (DMBA), ephedrine, and 1,3-DMAA itself. DMHA is a stimulant similar to dimethylamylamine (DMAA), which is banned by many sports bodies and governments due to safety concerns. DMHA is structurally similar to DMAA.

In the dietary supplement marketplace, DMHA is sold primarily in powder and capsule form, often as a component of multi-ingredient pre-workout or fat-burning formulas. DMHA is a central nervous system stimulant developed in the 1950s for use as an inhalant to treat bronchitis, laryngitis, and other conditions. It was never approved for oral use, but in recent years, it has shown up as an ingredient in dietary supplements. DMHA is used most often in pre-workout, weight-loss, and "fat burner" (thermogenic) dietary supplement products because of its supposed benefits to suppress appetite and enhance energy.

2. Claimed Natural Sources and Their Scientific Status

Supplement manufacturers have claimed that DMHA is a naturally occurring constituent of several plant species; however, these claims have been extensively scrutinized. The latest among those pharmaceutical stimulants is 1,5-dimethylhexylamine (1,5-DMHA or octodrine), an ingredient in newly introduced sports and weight loss supplements with its "natural" origin being cited from Aconitum or Kigelia plants.

The natural occurrence of 1,5-DMHA has been cited as Aconitum kusnezoffii, Kigelia africana, Forsythia suspensa, Biophytum veldkampii, and geranium (Pelargonium graveolens). However, a rigorous 2018 study in the Journal of Pharmaceutical and Biomedical Analysis directly challenged all such claims. In order to validate the natural existence of 1,5-DMHA, two GC/MS methods were developed. One method involved using thick-film megabore capillary columns to analyze underivatized 1,5-DMHA; the second method was to determine enantiomeric distribution of 1,5-DMHA. Fifteen Aconitum or Kigelia plant samples originating from various locations were analyzed, and none of them contained 1,5-DMHA within the limit of detection (25 ng/mL) of the method.

Identification of synthetic artifacts confirmed the synthetic origin of octodrine. This finding is corroborated at the compound level: the presence of a reductive amination byproduct confirms its synthetic origin. All three aliphatic amines described in this fact sheet (DMAA, DMBA, and DMHA) have been marketed as natural products, but scientific proof for these claims is not available.

With respect to the specific claims about Juglans regia (walnut): Juglans regia is the English walnut tree. This compound is reportedly present in the bark, which was not in the food supply prior to 1994, so it is not considered a legitimate dietary ingredient source. Juglans regia seeds, or walnuts, are legitimate ingredients and are not reported to contain this compound.

With respect to Kigelia africana: DMHA is reportedly present in Kigelia africana fruit extract, which might make it legitimate if derived from the fruit. However, many Kigelia africana fruit extracts on the market appear to derive from bark.

The scientific consensus is that some products claim that DMHA comes naturally from aconite plants, but there is no clear evidence that DMHA can be found in these plants. DMHA found in dietary supplements is likely made in a lab rather than produced from natural sources.

3. Historical and Pharmaceutical Background

DMHA has a documented pharmaceutical history that precedes its emergence in the dietary supplement industry by several decades. It was originally developed in the United States as an aerosolized treatment for bronchitis, laryngitis, and other conditions. Initially approved by the FDA in 1946 as Eskay's Oralator, this inhaler appeared only in the 1949 edition of the Physicians' Desk Reference.

Its pharmacology was studied in the early 1950s, was investigated as an antitumor drug and used to be available as a nasal decongestant under the tradenames Vaporpac and Tickle Tackel Inhaler. The drug was previously approved for use by the Food and Drug Administration (FDA) as an inhalant (i.e., Vaporpac and Tickle Tackle Inhaler) and in Germany as an oral medication as part of a multi-component medication (i.e., Ambredin and Ordinal), but is no longer available.

Octodrine was combined with several other medications, including theophylline, 3-octopamine, and adenosine, in multi-ingredient tablets sold between the early 1960s through the mid-2000s under the trade names Ambredin, Ordinal, Ordinal Retard, and Ordinal Forte. These multi-ingredient drugs were marketed for hypotension, asthma, and other conditions and were formulated to contain 8.2 mg, 16.5 mg, and 33 mg of octodrine as a free base. Octodrine was used for the treatment of hypotension.

The compound was then largely absent from legitimate medical markets for decades. With DMAA and AMP Citrate already phasing or phased out of current supplements, this drug was brought back on the market as an alternative in pre-workout and "fat-burner" products in 2016. According to a review paper published in the journal Brain Sciences, DMHA was originally developed as a nasal decongestant in the 1950s, but had not been on the market for many decades. It was revived in recent years by product formulators seeking new sources of stimulants in the wake of the banning of ephedra and DMAA.

There is no traditional ethnobotanical use of DMHA as a distinct compound. Because there is no clear evidence that DMHA can be found in aconite plants, and DMHA found in dietary supplements is likely made in a lab rather than produced from natural sources, any narrative of "traditional herbal use" of DMHA specifically is not supported by the peer-reviewed literature. The compound's documented history is pharmaceutical and industrial, not ethnobotanical.

4. Key Constituents, Active Compound, and Mechanisms of Action

As a single synthetic molecule, DMHA (octodrine) does not contain a plurality of "constituents" in the sense that botanical extracts do. Its pharmacological activity resides in the parent molecule itself, 1,5-dimethylhexylamine (or its isomers).

4.1 Sympathomimetic and Catecholaminergic Mechanism

Octodrine is the trade name for Dimethylhexylamine (DMHA), a central nervous stimulant that increases the uptake of dopamine and noradrenaline. Sympathomimetic effects of DMHA were explained as alpha adrenergic agonist-mediated via G-protein-coupled receptors (GPCRs).

The precise molecular pharmacology draws from DMHA's structural relationship to endogenous monoamine neurotransmitters. In the case of DMAA and its structural relatives like DMHA, they share a similar structure and are able to release both dopamine and norepinephrine through activation of trace amine associated receptor 1, while temporarily preventing their reuptake into the presynaptic terminal. These monoamines, most notably dopamine and norepinephrine, are responsible for exerting many of the common effects that stimulants produce — including enhanced euphoria and wakefulness (alertness), respectively.

In humans, the sympathomimetic effects of octodrine have been demonstrated to be bronchospasmolytic and hypertensive, whereas animal experiments have demonstrated the stimulation of the central nervous system, a local anesthetic effect, an increase in the pain threshold, and potential cardiotoxicity.

4.2 Vasoconstrictor Action

It is described as a sympathomimetic, vasoconstrictor, and local anesthetic. Vasoconstriction in the nasal mucosa was the basis for its original pharmaceutical application as a decongestant. In the context of dietary supplement use, DMHA also has vasoconstrictive properties, which means it can cause blood vessels to narrow, resulting in increased blood pressure.

4.3 Metabolite

Heptaminol is an active metabolite of octodrine. Heptaminol is itself a known cardiovascular stimulant, and its production during metabolism of DMHA may contribute to the compound's overall cardiovascular effect profile.

5. Scientific Evidence by Area of Use

5.1 Overall State of the Evidence

A foundational limitation affecting all evidence below is the near-total absence of modern, controlled human clinical trials. Crucially, there are almost no robust, modern, placebo-controlled human trials assessing octodrine's safety or efficacy. The first and most comprehensive modern review of octodrine, a 2018 cross-sectional study published in Brain Sciences by Catalani et al. at the University of Hertfordshire, confirmed this: their work provided the first observational cross-sectional analytic study on octodrine as a new drug trend after a gap spanning seven decades. A comprehensive multilingual assessment of literature, websites, drug fora, and other online resources was carried out with no time restriction in English, German, Russian, and Arabic. Keywords included Octodrine's synonyms and chemical isomers. Only five relevant publications emerged from the literature search, with most of the available data on bodybuilding websites and fora.

The paucity of the available literature, absence of review articles, systematic reviews, and meta-analytical studies clearly limit the extent of this present review. The sympathomimetic effect of octodrine is well-understood. However, the central effects including the psychostimulant and anti-obesity effects are not adequately explored and/or reported, with no formally documented experimental studies nor case reports.

5.2 Respiratory / Decongestant Use (Historical Pharmaceutical Evidence)

The strongest historical evidence for DMHA relates to its pharmaceutical application as a decongestant and bronchospasmolytic agent. DMHA is a central nervous system stimulant developed in the 1950s for use as an inhalant to treat bronchitis, laryngitis, and other conditions. In humans, the sympathomimetic effects of octodrine have been demonstrated to be bronchospasmolytic and hypertensive. These effects supported its historical pharmaceutical marketing in Germany under the Ambredin brand for asthma and other respiratory conditions.

However, this evidence is entirely historical. It was one component of a combination inhaler, registered under the name "Vaporpac," approved by the FDA in the 1960s. However, octodrine is not currently available in the US in "Vaporpac" or any other formulations. Octodrine is not included in FDA-approved medications for any medical condition. The available human evidence in this domain is limited to studies conducted during the mid-20th century, and no modern randomized controlled trial has evaluated DMHA as a decongestant or bronchodilator.

5.3 Athletic Performance and Pre-Workout Use

DMHA is used most often in pre-workout, weight-loss, and "fat burner" (thermogenic) dietary supplement products because of its supposed benefits to suppress appetite and enhance energy. It has also been claimed to enhance focus, memory, and attention; increase pain threshold; and decrease rates of perceived exertion.

Evidence quality: No adequate human clinical trials exist. Octodrine is an ingredient acting in a very similar manner to the popular DMAA, a central nervous stimulant shown to increase the uptake of dopamine and noradrenaline. For most of these compounds, the authors were unable to find any human studies supporting their claims, with only in vitro and/or animal studies reported.

The claimed benefits of enhanced focus and energy are extrapolated from the known catecholaminergic mechanism of action and from historical pharmaceutical data in limited human subjects, not from controlled modern trials in athletes or healthy exercising adults. People use DMHA for athletic performance, obesity, and other conditions, but there is no good scientific evidence to support these uses.

5.4 Weight Loss and Appetite Suppression

Reference to its multiple medicinal properties was found in five papers, which highlighted its sympathomimetic and bronchospasmolytic effects, with possible further actions as a stimulant, anti-obesity and appetite suppressant agent. These references to anti-obesity effects relate to the general class of sympathomimetic amines and not to dedicated clinical trials of DMHA for weight loss.

The central effects including the psychostimulant and anti-obesity effects are not adequately explored and/or reported, with no formally documented experimental studies nor case reports. Evidence quality: Preclinical and mechanistic inference only; no controlled human evidence is available.

5.5 Cardiovascular and Blood Pressure Effects

The effects of DMHA intake have been investigated in multiple preliminary studies on both humans and animals in the last century. Multiple animal studies have been published that investigated the effects of DMHA via intraperitoneal injection or inhalation in mice, rats, guinea pigs, rabbits, cats and dogs. The studies in mice and rats showed stimulation of the central nervous system. Larger animals showed an increase in blood pressure and cardiac output after DMHA administration. No minimal effect level could be derived for DMHA.

In animal studies, octodrine has been found to increase heart rate, myocardial contractility, and pain threshold. It has been studied in a dozen animal studies from the 1940s through the 1970s. These studies found that octodrine can increase blood pressure and cardiac output in animals.

In humans, the available evidence is limited to historical pharmaceutical observations, not placebo-controlled trials. Limited human data is available just from preliminary studies, while studies on activity and acute toxicity had been conducted on animals (cats, rabbits, dogs, and pigs). Evidence quality: Animal data only for most effects; human data limited to historical, uncontrolled pharmaceutical observations.

5.6 Central Nervous System Stimulation and Cognition

Effects include enhanced euphoria and alertness, and increased pain threshold, as reported in the limited animal and historical human literature. The claim of cognitive enhancement — enhanced focus, memory, and attention — has no foundation in controlled human clinical trials. There is limited research on the therapeutic benefits and harms associated with the use of octodrine. Evidence quality: Anecdotal and pharmacological inference; no human clinical evidence.

6. Body Systems Associated with DMHA

• Central Nervous System: Octodrine is a psychoactive central nervous system stimulant. Effects on dopamine and noradrenaline pathways underlie stimulant, mood-elevating, and alertness-promoting properties attributed to the compound.
• Cardiovascular System: Historically, octodrine was developed and sold as a nasal decongestant and circulatory stimulant. Early work in animals suggested that it could raise blood pressure, increase heart rate, and enhance cardiac output.
• Respiratory System: Octodrine was originally developed in the United States as an aerosolized treatment for bronchitis, laryngitis, and other conditions. The bronchospasmolytic effect was demonstrated in human pharmaceutical use.
• Metabolic / Adipose Tissue: Indirect stimulant-mediated thermogenic effects on metabolism have been claimed, but the anti-obesity effects are not adequately explored and/or reported, with no formally documented experimental studies nor case reports.
• Ocular (Glaucoma Risk): DMHA might have stimulant effects and cause blood vessels to constrict. This could worsen some types of glaucoma.

7. Dosage Forms and Reported Dosages

Dosage information for DMHA exists across two distinct historical contexts: mid-20th century pharmaceutical preparations and modern dietary supplement formulations. These figures should not be interpreted as evidence of safety or therapeutic efficacy.

7.1 Historical Pharmaceutical Dosages

Different doses of DMHA were used in the pharmaceutical tablets: Ambredin contained 8.2 mg, Ordinal Retard contained 16.5 mg, and Ordinal Forte contained 33 mg. These were part of multi-ingredient combination products used under medical supervision for hypotension and asthma.

7.2 Dosages Found in Modern Dietary Supplements

Nowadays, doses of up to 72 mg DMHA per serving are detected in dietary supplements. A quantitative analysis by Cohen et al. (2017), published in Clinical Toxicology, confirmed this: The multi-ingredient drugs were formulated to contain 8.2 mg, 16.5 mg, and 33 mg of octodrine as a free base compared to the 72 ± 7.5 mg of octodrine per serving found in the current study. This finding illustrates that the dosages commonly present in contemporary dietary supplements substantially exceed the doses used in the historical pharmaceutical preparations.

No New Dietary Ingredient Notification (NDIN) has ever been filed on this ingredient, nor are there any known GRAS (generally recognized as safe) affirmations. As a consequence, there is no scientifically or regulatorily established safe dosage range for oral human use.

8. Safety Considerations and Documented Interactions

8.1 FDA Regulatory Action

In the United States, the FDA considers DMHA to be an unsafe ingredient in dietary supplements. In 2019, the FDA issued nine warning letters to US manufacturers of dietary supplements containing DMHA as an unsafe food additive, deeming such products to be adulterated and illegal for marketing. In April 2019, the FDA issued nine warning letters to companies selling supplements containing DMHA, determining that it is either a "new dietary ingredient" lacking required safety notifications or an unsafe food additive.

FDA noted in the warning letters that DMHA does not tick off any of the boxes for being a legal dietary ingredient. There is no evidence that it was on the market prior to the DSHEA grandfather date of October 15, 1994. Failing that, there is no NDI notification on file for the ingredient. And the agency said it does not appear that any company or individual has compiled a GRAS dossier on the ingredient, whether self-affirmed or one that has been submitted to the agency.

Product recalls have occurred on the basis of DMHA's presence. TruVision Health LLC recalled dietary supplement products because they contained the unapproved dietary ingredients hordenine and/or octodrine/DMHA (1,5-Dimethylhexylamine).

8.2 Cardiovascular Risks

Use of DMHA can elevate blood pressure and could contribute to cardiovascular problems, including heart attack, shortness of breath, and tightening of the chest. The latest research from animal studies suggests DMHA might cause adverse cardiovascular effects. In addition, the same concerns associated with other stimulants apply to DMHA.

DMHA is possibly unsafe when taken by mouth. DMHA might cause side effects similar to dimethylamylamine (DMAA), including heart attack and death. This concern is grounded in class-based pharmacological inference, given that DMAA has been implicated in serious cardiovascular adverse events, and DMHA belongs to the same structural and mechanistic class.

8.3 Reported Side Effects

Reported side effects of octodrine include hypertension, dyspnea, and hyperthermia. The 2018 Catalani et al. cross-sectional review in Brain Sciences found that side effects included mood swings, tremor, concentration deficiency, over-stimulation, energy crashes, anxiety, high blood pressure, dyspnoea, rapid heartbeat, and heartburn that were reported in the six to eight hours after ingestion.

These adverse events are more likely to occur in sensitive sub-populations of people such as pregnant women and consumers with cardiovascular disease.

8.4 Special Populations

High blood pressure: DMHA might have stimulant effects and increase blood pressure; use should be avoided. Glaucoma: DMHA might have stimulant effects and cause blood vessels to constrict. This could worsen some types of glaucoma. Surgery: DMHA might have stimulant effects that could interfere with anesthesia and hemodynamic management. Individual sensitivity to stimulants also varies widely. Factors such as body weight, genetics, cardiovascular health, concurrent medications, and other lifestyle stimulants (like caffeine) will all influence how someone reacts.

8.5 Absence of Established Safe Dosing Parameters

Regulatory agencies have taken a clear stance that octodrine (DMHA) is not an approved dietary ingredient and that supplements containing it are adulterated or otherwise unlawful. From that perspective, any dose used in a supplement is considered problematic, because the ingredient itself is not recognized as safe. From a medical safety standpoint, the absence of robust human data means that no dose can be confidently described as safe for the general population.

8.6 Label Concealment and Adulteration

DMHA has also been found as an adulterant in sports supplements and is sold online as a designer drug. Manufacturers sometimes use obscure synonyms or botanical names on labels to avoid detection. Unscrupulous marketers will label products as containing the botanical ingredient Aconitum kusnezoffii when really the products contain the synthetic 2-aminoisoheptane. This represents a direct risk to consumers who may unknowingly ingest DMHA.

8.7 Anti-Doping Status

Categorized as a stimulant under the World Anti-Doping Prohibited List, octodrine is prohibited in-competition. Octodrine is on the WADA list as "Octodrine (1,5-dimethylhexylamine)" in the 2023 list published in late 2022. More than 80 stimulants are prohibited by WADA including now notorious drugs like methylhexaneamine (DMAA), DMBA, Octodrine (DMHA), nootropics like phenylpiracetam, and chemicals like strychnine.

DMHA gained popularity in pre-workouts and fat burners but was banned in Australia from October 1st, 2017. DMHA is now classified as a Schedule 10 poison and is no longer used by any reputable Australian manufacturers. DMHA is on the DoD Prohibited Dietary Supplement Ingredients list.

Octodrine is prohibited in-competition. Because clearance times depend on many individual factors, USADA cannot advise athletes on when they should discontinue using a substance to ensure that it has completely "washed out" from their body. Octodrine is not included in FDA-approved medications for any medical condition, so USADA would not grant a Therapeutic Use Exemption (TUE) for a product containing the substance.

8.8 Regulatory Context: Pattern of DMAA-Analog Substitution

DMHA's introduction into the supplement market followed a well-documented pattern of regulatory arbitrage. In the past years, there has been a mounting trend toward the addition of sympathomimetic stimulants in sports and weight loss supplements sold in the US and claimed to be from natural constituents. Whenever one stimulant is prohibited as an ingredient, some manufacturers or distributors might elect to substitute chemically similar compounds in commercial products. Shortly after 1,3-DMAA was banned, 1,3-dimethylbutylamine (1,3-DMBA), an analog of 1,3-DMAA, was formulated as an active ingredient in many supplements. In 2015, the FDA took action to remove 1,3-DMBA from the supplements because it did not meet the conditions to be lawfully marketed as a dietary ingredient in the US. DMHA followed as the next iteration in this substitution cycle.

References

• Catalani V, Prilutskaya M, Al-Imam A, et al. Octodrine: New Questions and Challenges in Sport Supplements. Brain Sciences. 2018;8(2):34. doi:10.3390/brainsci8020034 — PubMed Central (PMC)
• Catalani V et al. Octodrine: New Questions and Challenges in Sport Supplements — PubMed Abstract
• Wang M, Haider S, Chittiboyina AG, Parcher JF, Khan IA. 1,5-Dimethylhexylamine (octodrine) in sports and weight loss supplements: Natural constituent or synthetic chemical? J Pharm Biomed Anal. 2018;152:298–305 — ScienceDirect
• Cohen PA, Travis JC, Keizers PHJ, Deuster P, Venhuis BJ. Four experimental stimulants found in sports and weight loss supplements: 2-amino-6-methylheptane (octodrine), 1,4-DMAA, 1,3-DMAA and 1,3-DMBA. Clinical Toxicology. 2017;56(6):421–426 — ResearchGate
• DMHA (octodrine) in dietary supplement products — Operation Supplement Safety (OPSS), U.S. Department of Defense
• Is Octodrine Allowed in Sport? — U.S. Anti-Doping Agency (USADA)
• Govvi WOW! contains hidden ingredients (DMHA/1,4-DMAA) — U.S. Food and Drug Administration (FDA)
• TruVision Health Recalls Dietary Supplement Products Because of Possible Health Risk — U.S. Food and Drug Administration (FDA)
• Octodrine — Wikipedia (with primary literature citations)
• Fact sheet: DMAA, DMBA and DMHA in supplements — Rijksinstituut voor Volksgezondheid en Milieu (RIVM), National Institute for Public Health and the Environment, Netherlands
• Classification of octodrine — Medsafe (New Zealand Medicines and Medical Devices Safety Authority)
• Octodrine — National Center for Advancing Translational Sciences (NCATS) Inxight Drugs
• New Hidden Stimulants Surface in Sports Dietary Supplements — Nutritional Outlook
• FDA sends warning letters on illegal ingredients in sports, weight loss products — NutraIngredients
• Dietary Supplement Ingredient Advisory List — Banned Substances Control Group (BSCG)
• Dimethylhexylamine (DMHA) — NIH Dietary Supplement Label Database (DSLD)