Classification of 1,3-Dimethylamylamine (DMAA)

Completion Date: Classification Decision:

2011-07-08 Drug subject to the Food and Drug Regulations

On February 24, 2011, Health Canada commenced an extensive review of the literature, and consulted internally and externally with the Office of Controlled Substances within Health Canada, the U.S. Anti-Doping Agency and the U.S. Food and Drug Administration concerning the classification of DMAA. To date, no product containing DMAA has received market authorization from Health Canada as a human or veterinary drug.

Characterization of the Substance: Proper Name(s): 1,3-Dimethylamylamine; 1,3-dimethylpentylamine; 2-amino-4-methylhexane; 4-methyl-2hexylamine; 4-methylhexan-2-amine (NLM 2011). Common Name(s): Methylhexanamine; Geranamine; Forthan; Forthane (NLM 2011). Chemical Formula: C7H17N Structure:
H2N CH3 CH3 CH3

Molecular weight: 115.22 CAS #: 105-41-9

Discussion: DMAA is used in party pills, often as a replacement for benzylpiperazine (BZP). It is also used in fat-burning supplements and in sports nutritional supplements, especially those for bodybuilding (Geyer et al. 2008). DMAA is included on the World Anti-Doping Agencys Page 1 of 4

prohibited substance list as a stimulant (Deventer et al. 2011) under the name dimethylpentylamine, and is prohibited in competition. On November 15, 2010, the Canadian Centre for Ethics in Sport (CCES) advised athletes and support personnel that supplements containing the banned stimulant methylhexaneamine are widely available in the Canadian market and have been the source of many doping violations worldwide over the previous year. DMAA is an amine possessing adrenergic properties (ONeil et al. 2009). Allegedly considered for use in the treatment of nasal congestion by Eli Lily and company, this ingredient has been associated with a dietary supplement prepared by an Illinois chemist involved in a steroid scandal in the United States, and has been described as an amphetamine-like substance that would be undetectable in current sports drug tests (Shipley 2006). Since that time however, the detection and quantification of DMAA in urine specimens of male athletes has successfully been performed (Perrenoud et al. 2009). DMAA has only been reported in one scientific publication to be found in geranium oil, as separated and identified using capillary gas chromatography/mass spectrometry (Ping et al. 1996). However, a closer look at the article by Ping et al. (1996), most likely the one cited in Shipley (2006) as the Chinese research paper, revealed that the compound identified as DMAA in Chinese was reported with the molecular formula (C7H17N) and molecular weight (115). However, several discrepancies were noted in the paper including an incorrect English translation as the compound was described as 4-methyl-2-hexanamide in English and 4-methyl-2 hexaneamine in Chinese characters. A positional isomer was also reported as 5-methyl-2hexanamide, however the Chinese text reported this as 5-methyl-2-hexanamine, with a molecular weight corresponding to the amide (M.W. 129), yet the molecular formula was inconsistent with either the amide or the amine. Although the chemical content of geranium oil is known to be variable, other studies have failed to identify the presence of DMAA (Prasad et al. 2008, Jalali-Heravi et al. 2006, Peterson et al. 2006, Babu and Kaul 2005, Vernin et al. 2004, Rajeswara Rao et al. 2002, Jain et al. 2001).

Conclusion: Given the errors in the Ping et al. (1996) paper and the fact that these authors did not fully isolate and characterize DMAA, together with the contradictory information from numerous other peerreviewed scientific studies which show no natural occurrence, NHPD and TPD have jointly concluded that there is no credible scientific evidence that DMAA is captured as an isolate of a plant in Item 2 of Schedule 1 to the Natural Health Products Regulations (Government of Canada 2011a) and therefore cannot be classified as an NHP. For that reason, when manufactured, sold or represented for use in the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its symptoms, in human beings or animals, restoring, correcting or modifying organic functions in human beings or animals, or disinfection in premises in which food is manufactured, prepared or kept, DMAA is classified as a drug subject to the Food and Drug Regulations (Government of Canada 2011b).

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In addition, DMAA is not considered to be an acceptable non-medicinal ingredient in drugs or NHPs or as a food additive due to its pharmacological activity. Any product containing DMAA requires authorization by Health Canada as drug in order to be sold legally in Canada.

References: Babu KGD, Kaul VK. 2005. Variation in essential oil composition of rose-scented geranium (Pelargonium sp.) distilled by different distillation techniques. Flavour and Fragrance Journal 20: 222-231. Deventer K, Roels K, Delbeke FT, Van Eenoo P. 2011. Prevalence of legal and illegal stimulating agents in sports. Anal. Bioanl. Chem. DOI 10.1007/s00216-011-4863-0. Published online only, April 09, 2011. Geyer H, Parr MK, Koehler K, Mareck U, Schanzer W, Thevis M. 2008. Nutritional supplements cross-contaminated and faked with doping substances. J. Mass. Spectrum 43: 892902. Government of Canada 2011a. Natural Health Products Regulations. URL: http://lawslois.justice.gc.ca/eng/regulations/SOR-2003-196/index.html [Accessed 2011-07-07]. Government of Canada 2011b. Food and Drug Regulations. URL: http://lawslois.justice.gc.ca/eng/regulations/C.R.C.,_c._870/index.html [Accessed 2011-07-07]. Jain N, Aggarwal KK, Syamasundar KV, Srivastava SK, Kumar S. 2001. Essential oil composition of geranium (Pelargonium sp.) from the plains of Northern India. Flavour and Fragrance Journal 16: 44-46. Jalali-Heravi M, Zekavat B, Sereshti H. 2006. Characterization of essential oil components of Iranian geranium oil using gas chromatography-mass spectrometry combined with chemometric resolution techniques. Journal of Chromatography A 1114: 154-163. NLM: U.S. National Library of Medicine ChemIDPlus Advanced. 2011. Methylhexaneamine. URL: http://chem.sis.nlm.nih.gov/chemidplus/ [Accessed 2011-07-07]. ONeil MJ, Heckelman PE, Koch CB, Roman KJ (eds). 2009. The Merck Index: an Encyclopedia of Chemicals, Drugs, and Biologicals, Fourteenth Edition (2006). Merck & Co. Inc., Whitehouse Station, NJ, USA. Electronic version [Accessed 2010-01-29]. Perrenoud L, Saugy M, Saudan C. 2009. Detection in urine of 4-methyl-2-hexaneamine, a doping agent. Journal of Chromatography B 877(29): 3767-3770. Peterson A, Machmudah S, Roy BC, Goto M, Sasaki M, Hirose T. 2006. Extraction of essential oil from geranium (Pelargonium graveolens) with supercritical carbon dioxide. J. Chem. Technol. Biotechnol. 81: 167-172. Page 3 of 4

Ping Z, Jun Q, Qing L. 1996. A study on the chemical constituents of geranium oil. Journal of Guizhou Institute of Technology 25(1): 8285. Prasad A, Chattopadhyay A, Yadav A, Kumari R. 2008. Variation in the chemical composition and yield of essential oil of rose-scented geranium (Pelargonium sp.) by the foliar application of metallic salts. Flavour and Fragrance Journal 23: 133-136. Rajeswara Rao BR, Kaul PN, Syamasundar KV, Ramesh S. 2002. Water soluble fractions of rose-scented geranium (Pelargonium species) essential oil. Bioresource Technology 84: 243246. Shipley A. 2006. Chemists new product contains hidden substance. Washington Post, Monday, May 8th. Washington, DC. Vernin GA, Chakib S, Vernin GMF, Zamkotsian RM. 2004. Geranium (Pelargonium sp.) essential oil from Reunion. Minor compounds: acids, phenols, pyridines. J. Essent. Oil Res. 16: 26-28.

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