![]() | |
![]() | |
Clinical data | |
---|---|
Other names | Methylhexaneamine, methylhexamine, geranamine, geranium extract, geranium oil, 2-amino-4-methylhexane, dimethylamylamine, DMAA, 1,3-dimethylamylamine, 1,3-DMAA, 1,3-dimethylpentylamine, 4-methyl-2-hexanamine, 4-methyl-2-hexylamine |
Routes of administration | Nasal spray, oral |
ATC code |
|
Legal status | |
Legal status | |
Pharmacokinetic data | |
Elimination half-life | ~8.5 hours |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.002.997 |
Chemical and physical data | |
Formula | C7H17N |
Molar mass | 115.220 g·mol−1 |
3D model (JSmol) | |
| |
| |
![]() ![]() |
Methylhexanamine (also known as methylhexamine, 1,3-dimethylamylamine, 1,3-DMAA, dimethylamylamine, and DMAA; trade names Forthane and Geranamine) 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and developed by Eli Lilly and Company and marketed as an inhaled nasal decongestant from 1948 until it was voluntarily withdrawn from the market in the 1980s. [7]
Since 2006 methylhexanamine has been sold extensively under many names as a stimulant or energy-boosting dietary supplement under the claim that it is similar to certain compounds found in geraniums, but its safety has been questioned as a number of adverse events and at least five deaths have been associated with methylhexanamine-containing supplements. [8] It is banned by many sports authorities and governmental agencies. Despite multiple warning letters from the FDA, [9] as of 2019, the stimulant remains available in sports and weight loss supplements in the US. [10]
In April 1944, Eli Lilly and Company introduced methylhexanamine under the brand name Forthane as an inhaled nasal decongestant; Lilly voluntarily withdrew methylhexanamine from the market in 1983. [11] : 12 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; octin and oenethyl were eventually approved for use in keeping blood pressure sufficiently high for patients under anesthesia.[ citation needed ]: 95–96
Patrick Arnold reintroduced methylhexanamine in 2006 as a dietary supplement, [12] [13] 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. A large number of supplements focusing on fat loss and workout energy (thermogenic or general-purpose stimulants) used the ingredient in concert with other substances such as caffeine, a combination similar to the combination of ephedrine and caffeine.
Methylhexanamine-containing supplements sometimes list "geranium oil" or "geranium extract" as a source of methylhexanamine. However, geranium oils do not contain methylhexanamine, and the methylhexanamine in these supplements is added in the form of synthetic material. [14] A variety of studies have explored the possibility that DMAA is found in some types of geraniums, but at present, high quality evidence of DMAA's presence in plants is lacking. [15] [16]
Methylhexanamine is synthesized by reacting 4-methylhexan-2-one with hydroxylamine, which converts the 4-methylhexan-2-one to 4-methylhexan-2-one oxime, which is reduced via catalytic hydrogenation; the resulting methylhexanamine can be purified by distillation. [17] : 995–996
Methylhexanamine is an indirect sympathomimetic drug that constricts blood vessels and thus has effects on the heart, lungs, and reproductive organs. It also causes bronchodilation, inhibits peristalsis in the intestines, and has diuretic effects. Most studies have been done on pharmacological effects when the drug is inhaled; the understanding of what methylhexanamine does when taken orally are mostly based on extrapolating from the activities of similar compounds.: 97 A 2013 review concluded that: "Pharmacological effects after oral intake can be expected on the lungs (bronchodilation) and the nasal mucosa following a single oral dose of about 4–15 mg. Pharmacological effects on the heart can be expected following a single oral dose of about 50–75 mg. Pharmacological effects on the blood pressure can be expected after a single oral dose of about 100 mg. Because of the long half-life, there is a risk that repeated doses within 24–36 hours could lead to steadily stronger pharmacological effects (build-up).": 98
Methylhexanamine may be quantified in blood, plasma, or urine by gas or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma methylhexanamine concentrations are expected to be in a range of 10–100 μg/L in persons using the drug recreationally, >100 μg/L in intoxicated patients, and >300 μg/L in victims of acute overdosage. [18] [19]
The LD50 for methylhexanamine is 39 mg/kg in mice and 72.5 mg/kg in rats, when administered intravenously.: 95 [20] : 110
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". [21] Numerous adverse events and at least five deaths have been reported in association with methylhexanamine-containing dietary supplements. [8] There have also been reports of secondary open-angle glaucoma related to methylhexanamine supplementation. [22]
A 2012 review by a panel convened by the U.S. Department of Defense to study whether the military should ban methylhexanamine supplements from stores on its bases concluded that: "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. Without further rigorous study designs developed to evaluate the safety of DMAA, especially in patients with concomitant use of other substances, co-morbid conditions and high frequency use, the magnitude of the association of DMAA with adverse medical events is uncertain. 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, resulting in consequential impact to some Service members and other beneficiaries. DMAA should be further studied to evaluate its safety. Data from the case control study suggest that the frequency and amount of DMAA use and risk of specific [acquired medical events], particularly heat injuries and rhabdomyolysis, need to be examined in greater detail. ... The Safety Review Panel recommended ... to continue the prohibition of sales of DMAA-containing products in Exchanges and concessions. The Panel judged that the evidence supports sufficient risk, even if very low, of another death or catastrophic illness of a Service member who has used DMAA-containing products, without any offsetting benefit of these products." [11] : 10
In 2010, a 21-year-old man in New Zealand presented with a cerebral hemorrhage after ingesting 556 mg of methylhexanamine, caffeine, and alcohol. [23] Health authorities in Hawaii linked cases of liver failure and one death to OxyElite Pro, a weight loss and bodybuilding dietary supplement. [24]
The death of Claire Squires, a runner who collapsed near the finish-line of the April 2012 London Marathon, has been linked to methylhexanamine. The coroner stated that methylhexanamine was "probably an important factor" during the inquest. Despite, according to a friend, having been diagnosed with an irregular heartbeat [25] and advised not to consume methylhexanamine, it is believed that she consumed the substance through drinking an energy drink, which was subsequently reformulated to exclude methylhexanamine. [26]
A number of sporting authorities and countries have banned or heavily restricted the use of methylhexanamine as a dietary supplement, due to serious concerns about its safety. These countries include Australia, Brazil, Canada, Finland, New Zealand, Sweden, Switzerland, the United Kingdom, and the United States.
Many professional and amateur sports bodies, such as the World Anti Doping Agency, have banned methylhexanamine as a performance-enhancing substance and suspended athletes that have used it. [27] [28] [29] [30] [31] [32]
In 2010, the US military issued a recall of all methylhexanamine-containing products from all military exchange stores worldwide. [51] [52]
In July 2011, Health Canada decided methylhexanamine was not a dietary substance, but was a drug requiring further approval. Consequently, Health Canada banned all sales of methylhexanamine. [53]
In June 2012, the National Food Agency of Sweden issued a general warning regarding use of methylhexanamine products, resulting in a sales ban in parts of the country. [54]
In July 2012, the National Health Surveillance Agency of Brazil issued a warning to the general public on the hazards of products that contain methylhexanamine. [55] It also updated the list of prohibited substances to insert methylhexanamine, which translates into the banishment of products containing such ingredient from the Brazilian market. [56]
In 2012, Australia banned methylhexanamine. In New South Wales, methylhexanamine was classed as a "highly dangerous substance" on the poisons list. [57]
In August 2012, the UK Medicines and Healthcare products Regulatory Agency (MHRA) has ruled that the popular DMAA containing sports supplement Jack3D is an unlicensed medicinal product and that it and all other methylhexanamine containing products need to be removed from the UK market amid concerns of potential risks to public safety. [58]
In 2012 the New Zealand Ministry of Health banned the sale of methylhexanamine products, [59] due in part to its growing recreational use as party pills. [60] [61]
In April 2013, the US Food and Drug Administration determined that methylhexanamine was potentially dangerous and did not qualify as a legal dietary supplement; it warned supplement makers that it was illegal to market methylhexanamine and warned consumers of potentially serious health risks associated with methylhexanamine-containing products. [8] [62] The FDA has issued warning letters to manufacturers and distributors who continued to market products containing methylhexanamine. [63]
A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources, or that are synthetic. The classes of nutrient compounds in supplements include vitamins, minerals, fiber, fatty acids, and amino acids. Dietary supplements can also contain substances that have not been confirmed as being essential to life, and so are not nutrients per se, but are marketed as having a beneficial biological effect, such as plant pigments or polyphenols. Animals can also be a source of supplement ingredients, such as collagen from chickens or fish for example. These are also sold individually and in combination, and may be combined with nutrient ingredients. The European Commission has also established harmonized rules to help insure that food supplements are safe and appropriately labeled.
Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection it lasts about an hour and when taken by mouth it can last up to four hours.
Ephedra is a medicinal preparation from the plant Ephedra sinica. Several additional species belonging to the genus Ephedra have traditionally been used for a variety of medicinal purposes, and are a possible candidate for the soma plant of Indo-Iranian religion. It has been used in traditional Chinese medicine, in which it is referred to as Ma Huang, for more than 2,000 years. Native Americans and Mormon pioneers drank a tea brewed from other Ephedra species, called "Mormon tea" and "Indian tea".
Nootropics, colloquially brain supplements, smart drugs and cognitive enhancers, are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.
Adrafinil, sold under the brand name Olmifon, is a wakefulness-promoting medication that was formerly used in France to improve alertness, attention, wakefulness, and mood, particularly in the elderly. It was also used off-label by individuals who wished to avoid fatigue, such as night workers or others who needed to stay awake and alert for long periods of time. Additionally, the medication has been used non-medically as a novel vigilance-promoting agent.
Sibutramine, formerly sold under the brand name Meridia among others, is an appetite suppressant which has been discontinued in many countries. It works as a serotonin–norepinephrine reuptake inhibitor similar to a tricyclic antidepressant. Until 2010, it was widely marketed and prescribed as an adjunct in the treatment of obesity along with diet and exercise. It has been associated with increased cardiovascular diseases and strokes and has been withdrawn from the market in 2010 in several countries and regions including Australia, Canada, China, the European Union, Hong Kong, India, Mexico, New Zealand, the Philippines, Thailand, the United Kingdom, and the United States. However, the drug remains available in some countries.
Velvet antler is the whole cartilaginous antler in a precalcified growth stage of the Cervidae family including the species of deer such as elk, moose, and caribou. Velvet antler is covered in a hairy, velvet-like "skin" known as velvet and its tines are rounded, because the antler has not calcified or finished developing.
Party pills, also known as "herbal highs", "pep pills" "dance pills" and "natural power", is a colloquialism for a type of recreational drug whose main ingredient was originally benzylpiperazine (BZP), but has expanded to a wide range of compounds with a variety of effects. BZP is banned in several countries, including the USA, Republic of Ireland, Australia and New Zealand, but is available on a more or less restricted basis in many jurisdictions. A range of other piperazine derivatives have also been sold as ingredients in party pills, and many of these branded "proprietary blends" have subsequently been sold in countries around the world.
β-Methylphenethylamine is an organic compound of the phenethylamine class, and a positional isomer of the drug amphetamine, with which it shares some properties. In particular, both amphetamine and β-methylphenethylamine are human TAAR1 agonists. In appearance, it is a colorless or yellowish liquid.
Fastin is a dietary supplement that is manufactured and marketed for weight loss by Hi Tech Pharmaceuticals in Atlanta, GA. There is no clinical evidence that this supplement is effective for weight loss. Fastin was once a brand name of a drug called phentermine and the Fastin brand of phentermine was manufactured by King Pharmaceuticals.
Pavle Jovanovic was an American bobsledder of Serbian origin who had competed since 1997. At the 2006 Winter Olympics in Turin, he finished seventh both in the two-man event and in the four-man event. Although on the U.S. Bobsled team in 2002, he was disqualified from competing due to the presence of prohibited substances from food supplements, which he claimed were taken without his knowledge or intent.
Phenpromethamine, also known as N,β-dimethylphenethylamine, is a sympathomimetic nasal decongestant of the phenethylamine group. It was previously marketed as a nasal inhaler from 1943 through 1960 but is no longer available. The medication is a stimulant and is banned by the World Anti-Doping Agency. It has been detected in dietary supplements starting in the 2010s.
Octodrine is a stimulant drug whose pharmacology was 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. The drug was previously approved for use by the FDA as an inhalant and in Germany as an oral agent as part of a multicomponent medication, but is no longer available.
The regulation of food and dietary supplements by the U.S. Food and Drug Administration is a process governed by various statutes enacted by the United States Congress and interpreted by the U.S. Food and Drug Administration ("FDA"). Pursuant to the Federal Food, Drug, and Cosmetic Act and accompanying legislation, the FDA has authority to oversee the quality of substances sold as food in the United States, and to monitor claims made in the labeling about both the composition and the health benefits of foods.
Oxilofrine is a substituted phenethylamine stimulant drug chemically related to ephedrine and to synephrine.
A temporary class drug is a relatively new status for controlled drugs, which has been adopted in some jurisdictions, notably New Zealand and the United Kingdom, to attempt to bring newly synthesised designer drugs under legal control. The controlled drug legislation in these jurisdictions requires drug scheduling decisions to follow an evidence-based process, where the harms of the drug are assessed and reviewed so that an appropriate legal status can be assigned. Since many designer drugs sold in recent years have had little or no published research that could help inform such a decision, they have been widely sold as "legal highs", often for months, before sufficient evidence accumulates to justify placing them on the controlled drug schedules.
The Dietary Supplement Health and Education Act of 1994 ("DSHEA"), is a 1994 statute of United States Federal legislation which defines and regulates dietary supplements. Under the act, supplements are regulated by the FDA for Good Manufacturing Practices under 21 CFR Part 111. The act was intended to exempt the dietary and herbal supplement industry from most FDA drug regulations, allowing them to be sold and marketed without scientific backing for their health and medical claims.
1,3-Dimethylbutylamine, is a stimulant drug structurally related to methylhexanamine where a butyl group replaces the pentyl group. The compound is an aliphatic amine.
Pre-workout is a generic term for a range of bodybuilding supplement products used by athletes and weightlifters to enhance athletic performance. Supplements are taken to increase endurance, energy, and focus during a workout. Pre-workout supplements contain a variety of ingredients such as caffeine and creatine, differing by capsule or powder products. The first pre-workout product entered the market in 1982, and since then the category has grown in use. Some pre-workout products contain ingredients linked to adverse effects. Although these products are not regulated, the Food and Drug Administration (FDA) warns consumers to be cautious when consuming them.
Deterenol is a stimulant drug which acts as a beta agonist. It has been found as an ingredient of dietary supplement products, but is banned in most countries due to risk of cardiac arrest.
[Methylhexanamine] is not a dietary ingredient, and [Methylhexanamine]-containing products marketed as dietary supplements are illegal and their marketing violates the law.
DMAA is not an 'herb or other botanical.' It is not a 'constituent' of an herb or other botanical. And it is not generally recognized by qualified experts, as adequately shown through scientific procedures, to be safe under the conditions of its intended use.
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.