|PubChem||, (4S), (2R,4R), (2R,4S), (2S,4S), (2S,4R)|
|Jmol-3D images||Image 1|
|Molar mass||115.22 g mol−1|
|Appearance||white crystal powder|
|Boiling point||134 °C (273 °F; 407 K)|
|Solubility in water||soluble in water|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
Methylhexanamine, commonly known as 1,3-dimethylamylamine or DMAA, was invented and developed by Eli Lilly and Company and was marketed by Lilly as an inhaled nasal decongestant pharmaceutical drug from 1944 until Lilly voluntarily withdrew it from the market in 1983. Methylhexanamine is an indirect sympathomimetic drug.
Since 2006 methylhexanamine has been marketed extensively under many names as an 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 5 deaths have been associated with methylhexanamine-containing supplements. It has been banned by many sport authorities and governmental agencies.
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.: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 DMAA and four other similar compounds being brought to market for that use: tuaminoheptane, octin, oenethyl, and propylhexedrine; octin and oenethyl were eventually approved for use in keeping blood pressure sufficiently high for patients under anesthesia.:95–96
Marketing as dietary supplement
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. A large number of supplements focusing on fat loss and workout energy (thermogenic or general-purpose stimulants) now use the ingredient in concert with other substances such as caffeine, a combination similar to the combination of ephedrine and caffeine, which are marketed under trade names such as Floradrene, OxyElite, and Jack3d.
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. Recent studies have shown that DMAA is found in some types of geraniums.
Methylhexanamine is synthesized by reacting 4-methylhexanone-2 with hydroxylamine, which converts the 4-methylhexanone-2 to 4-methylhexanone-2 oxime, which is reduced with hydrogen by means of a catalyst; the resulting methylhexanamine can be purified by distillation.: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.:95 Most studies have been done on pharmacological effects when the drug is inhaled; our 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
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." Numerous adverse events and at least 5 deaths have been reported in association with methylhexanamine-containing dietary supplements.
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 AMEs, 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.":10
A 2012 review of the regulatory status of DMAA found that "1,3-Dimethylamylamine (DMAA) is a pressor amine often found in food supplements for athletes at dosages of 25-65 mg. Historically, the compound has been used as a nasal decongestant but its oral application is largely unstudied leaving the regulatory status of such food supplements as unlicensed medicines undetermined. We therefore reviewed the literature on DMAA and similar amines in order to deduce an effective oral dosage. Based on our findings we conclude that oral preparations with >4 mg DMAA per dose unit should be considered as effective as a bronchodilator. Food supplements that exceed that limit are in fact subject to the Medicines Act and require licensing. Dosages higher than 100-200 mg are expected to cause serious adverse events.":93
Deaths and injuries
In 2010 a 21-year-old male in New Zealand presented with a cerebral hemorrhage after ingesting 556 mg of methylhexanamine, caffeine, and alcohol. Health authorities in Hawaii linked cases of liver failure and one death to OxyElite Pro.
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 having, according to a friend, having been diagnosed with an irregular heartbeat - and advised not to consume methylhexanamine, it is believed that she consumed the substance through drinking an energy drink, which was subsequently adjusted to exclude methylhexanamine.
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 the U.S., Canada, New Zealand, Sweden, Australia, the United Kingdom, and Brazil.
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.
- On 19 June 2012, the South African Institute for Drug-Free Sport (SAIDS) confirmed the 2012 Comrades Marathon winner, Ludwick Mamabolo, tested positive for the banned stimulant. Mamabolo could face a two-year ban and be stripped of his title if found guilty by an independent tribunal.
- VFL player Matthew Clark was suspended for two years after the banned substance methylhexanamine was detected in his system after a game in 2011.
- On 8 August 2013, US Weightlifter Brian Wilhelm accepted a nine-month suspension after testing positive for methylhexaneamine in a urine sample from December 2012 at the American Open.
- MotoGP rider Anthony West was suspended for one month by the FIM International Disciplinary Court (CDI) on 29 October 2012 after testing positive for methylhexanamine on 20 May 2012 at the French Grand Prix. This was increased retroactively to an 18 month suspension, starting from 20 May 2012, on 28 November 2013 after an appeal by the World Anti-Doping Agency (WADA).
- In December 2013, boxer Brandon Rios, after losing a unanimous decision to Manny Pacquiao, was suspended by the China Professional Boxing Association after testing positive for the drug.
- During the 2014 Winter Olympics in Sochi, three athletes tested positive for methylhexanamine: bobsleigh brakeman and former decathlete William Frullani, German biathlete Evi Sachenbacher-Stehle and Latvian ice hockey forward Vitalijs Pavlovs.
- During the 2015 Asian Cup, Iraqi player Alaa Abdul-Zahra was subject to an investigation relating to illegal usage of Methylhexanamine. 
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. In April 2012, New Zealand formally banned methylhexanamine, citing its use in "party pills". 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.
In July 2012, the National Health Surveillance Agency (ANVISA) of Brazil issued a warning to the general public on the hazards of products that contain methylhexanamine. 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.
In 2012, Australia banned methylhexanamine. In New South Wales, methylhexanamine was classed as a "highly dangerous substance" on the poisons list.
In August 2012, the U.K. 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.
In April 2013, the U.S. 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. The FDA has issued warning letters to manufacturers and distributors who continued to market products containing methylhexanamine.
- "1,3-Dimethylpentylamine - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 26 March 2005. Identification and Related Records. Retrieved 27 May 2012.
- Singer, Natasha; Peter Lattman (April 16, 2013). "F.D.A. Issues Warning on Workout Supplement". New York Times. Retrieved April 16, 2013.
- Col John Lammie et al. Report of the Department Of Defense: 1,3 Dimethylamylamine (Dmaa) Safety Review Panel June 3, 2013
- Venhuis, Bastiaan J.; De Kaste, Dries (2012). "Scientific opinion on the regulatory status of 1,3-Dimethylamylamine (DMAA)". European Journal of Food Research & Review 2 (4): 93–100.
- Shipley, Amy (May 8, 2006). "Chemist's New Product Contains Hidden Substance". The Washington Post.
- Carroll, Will. (2010-08-16) Under The Knife: 997. Baseball Prospectus. Retrieved on 2012-04-12.
- Lisi A, Hasick N, Kazlauskas R, Goebel C (2011). "Studies of methylhexaneamine in supplements and geranium oil". Drug Test Anal 3 (11-12): 873–6. doi:10.1002/dta.392. PMID 22147493.
- Heather L. Fleming, Patricia L. Ranaivo and Paul S. Simone (2012). "Analysis and Confirmation of 1,3-DMAA and 1,4-DMAA in Geranium Plants Using High Performance Liquid Chromatography with Tandem Mass Spectrometry at ng/g Concentrations". Analytical Chemistry Insights (7): 59–78. doi:10.4137/ACI.S10445.
- "Methylhexaneamine Carbonate" entry in Marshall Sittig. Pharmaceutical Manufacturing Encyclopedia, Second Edition, Reprint Edition, Volume 1-2. 1988 Noyes Publications. Westwood, New Jersey.
- Miya TS, Edewards LD. A pharmacological study of certain alkoxyalkylamines. J Am Pharm Assoc Am Pharm Assoc (Baltim). 1953 Feb;42(2):107-10 PMID 13034643.
- "FDA challenges marketing of methylhexanamine products for lack of safety evidence: Agency cites ten companies in warning letters". United States Food and Drug Administration. April 27, 2012. Retrieved March 17, 2013.
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.
- Bloomer, RJ; Paul Gee, Suzanne Jackson, Josie Easton (6 December 2010). "Another bitter pill: a case of toxicity from DMAA party pills". Journal of the New Zealand Medical Association 39 (3): 111–20. doi:10.4137/NMI.S8566. PMID 22030947.
- Medical News & Perspectives: Dietary Supplement Linked to Cases of Acute Hepatitis, Bridget M. Kuehn, JAMA. 2013;310(17):1784. doi:10.1001/jama.2013.281868. November 6, 2013
- ["http://www.telegraph.co.uk/sport/othersports/athletics/london-marathon/9237808/Claire-Squires-runner-who-died-during-London-Marathon-suffered-from-heart-condition.html" Claire Squires: runner who died during London Marathon 'suffered from heart condition']
- "Claire Squires inquest: DMAA was factor in marathon runner's death". BBC News. 30 January 2013. Retrieved 30 January 2013.
- WADA 2010 Prohibited List (pdf), World Anti-Doping Agency, Monday, 19 September 2009
- "IAAF wait for Jamaica drug ruling". BBC Sport (BBC). August 11, 2009.
- "Rui Costa and his brother test positive". CyclingNews. CyclingNews. October 18, 2010.
- "Belgian amateur champion receives one-year ban". News. CyclingNews. December 9, 2010.
- "Minor Leaguer suspended 50 games". MLB.com (MLB.com). 2011-11-01. Retrieved 2011-11-01.
- "Doping: Sperren für Schweizer Aquathlet und Duathleten aus Portugal". DNF-is-no-option.com (DNF-is-no-option.com). 2012-02-16. Retrieved 2012-01-12.
- St Kilda's Ahmed Saad faces two-year drugs ban
- US Weightlifting Athlete, Wilhelm, Accepts Sanction For Anti-Doping Rule Violation http://www.usada.org/media/sanction-wilhelm8813 (2013-08-8)
- Anthony West loses results after Anti-Doping appeal http://www.crash.net/motogp/news/198653/1/moto2_anthony_west_erased_from_results.html
- Ronnie Nathanielsz (December 16, 2013). "Brandon Rios is Suspended By CPBO Until April 24th". BoxingScene.com. Retrieved 2013-12-16.
- "Evi Sachenbacher-Stehle and William Frullani sent home". BBC News (BBC). 21 February 2014. Retrieved 23 February 2014.
- "Two athletes expelled for doping". ESPN. 22 February 2014. Retrieved 23 February 2014.
- "DMAA products pulled from base shelves". Retrieved 24 January 2013.
- DMAA products pulled from base shelves – Military Off Duty, Army Health, military fitness, army physical fitness. Army Times. Retrieved on 2012-04-12.
- Rovell, Darren (2 May 2012). "DMAA Brands Start To Reformulate Products Without the Ingredient". CNBC. Retrieved 1 August 2012.
- "DMAA Banned from 9 April 2012". New Zealand: Ministry of Health. Retrieved 1 August 2012.
- "Varning för kosttillskott som innehåller DMAA".
- "Anvisa alerta para risco de consumo de suplemento alimentar, July 2012". Brazilian Government: National Health Surveillance Agency (ANVISA). Retrieved 22 January 2013.
- "Resolução de Diretoria Colegiada (RDC) no. 37, July 2012". Brazilian Government: National Health Surveillance Agency (ANVISA). Retrieved 22 January 2013.
- McNeilage, Amy (1 August 2012). "Drug in workout drinks to be illegal". The Sydney Morning Herald. Retrieved 1 August 2012.
- "Press release: MHRA to remove popular sports supplement used by international athletes from the market".
- New Zealand Ministry of Health. Dunne announces Temporary Class Drug Notice March 8, 2012
- "New pill ingredient worries ministry". Television New Zealand. October 4, 2008. Retrieved October 23, 2011.
- Steward, Ian (November 9, 2009). "Party pill inventor backs restriction". The Press. Retrieved October 23, 2011.
- "Stimulant Potentially Dangerous to Health, FDA Warns". U.S. Food and Drug Administration. April 11, 2013. Retrieved April 16, 2013.
- FDA Press Release. OxyElite Pro Dietary Supplements by USP Labs: Recall - Products Linked to Liver Illnesses November 10, 2013
- "Stimulant Potentially Dangerous to Health, FDA Warns". U.S. Food and Drug Administration. April 11, 2013.
- Bussel, Igor I; Pavlov Jr, Andrey A (June 7, 2013). "DMAA: Efficacious but is it Safe?". Science Based Medicine Blog.