Physiological and pharmacokinetic effects of oral 1,3-dimethylamylamine administration in men

Brian K Schilling, Kelley G Hammond, Richard J Bloomer, Chaela S Presley, Charles R Yates, Brian K Schilling, Kelley G Hammond, Richard J Bloomer, Chaela S Presley, Charles R Yates

Abstract

Background: 1,3-dimethylamylamine (DMAA) has been a component of dietary supplements and is also used within "party pills," often in conjunction with alcohol and other drugs. Ingestion of higher than recommended doses results in untoward effects including cerebral hemorrhage. To our knowledge, no studies have been conducted to determine both the pharmacokinetic profile and physiologic responses of DMAA.

Methods: 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 using high-performance liquid chromatography-mass spectrometry. Resting heart rate, blood pressure, and body temperature was also measured.

Results: One subject was excluded from the data analysis due to abnormal DMAA levels. Analysis of the remaining 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. Heart rate, blood pressure, and body temperature were largely unaffected by DMAA treatment.

Conclusions: These are the first data to characterize the oral pharmacokinetic profile of DMAA. 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. Finally, a single 25 mg dose of DMAA does not meaningfully impact resting heart rate, blood pressure, or body temperature.

Trial registration: NCT01765933.

Figures

Figure 1
Figure 1
Chromatogram of samples spiked at 20 ng/mL DMAA = 8.26 min and 8.56 min; 9.65 min = 2-aminoheptane.
Figure 2
Figure 2
Chromatogram for subject #8 at baseline; 1.5 ng/ml DMAA.
Figure 3
Figure 3
Chromatogram for subject #8 at 0.75 hrs post ingestion; 44 ng/ml DMAA.
Figure 4
Figure 4
Heart rate responses (BPM) after oral administration of 25 mg DMAA (n = 7). Data are mean ± SD. A significant time effect was noted (p < 0.000), but no pairwise differences were detected post-hoc (p > 0.05).
Figure 5
Figure 5
Blood pressure responses (mm Hg) after oral administration of 25 mg DMAA (n = 7). Data are mean ± SD. No significant time effects noted (p = 0.271 for diastolic blood pressure and p = 0.722 for systolic blood pressure).
Figure 6
Figure 6
Temperature (°F) after oral administration of 25 mg DMAA (n = 7). There was a significant time effect (p = 0.001) noted. * indicates 12-hour greater than 2 hr (p = 0.025). † indicates 12-hour greater than 3-hr (p = 0.009). Data are mean ± SD.
Figure 7
Figure 7
Individual and mean plasma concentration-time profiles after oral administration of 25 mg DMAA.

References

    1. U.S. Food and drug administration. .
    1. Miya TS, Edwards LD. A pharmacological study of certain alkoxyalkylamines. J Am Pharm Assoc. 1953;42:107–110.
    1. Merck. Monographs. In: Anonymous, editor. The Merck index. 12. New York: Merck; 1996. pp. 6166–6167.
    1. Stars and stripes. .
    1. Gee P, Tallon C, Long N, Moore G, Boet R, Jackson S. Use of recreational drug 1,3-dimethylethylamine (DMAA) associated with cerebral hemorrhage. Ann Emerg Med. 2012;60(4):431–434. doi: 10.1016/j.annemergmed.2012.04.008.
    1. Gee P, Jackson S, Easton J. Another bitter pill: a case of toxicity from DMAA party pills. N Z Med J. 2010;123(1327):124–127.
    1. Bloomer RJ, McCarthy CG, Farney TM, Harvey IC. Effect of caffeine and 1,3-dimethylamylamine on exercise performance and blood markers of lipolysis and oxidative stress in trained men and women. J Caffeine Res. 2011;1(3):169–177. doi: 10.1089/jcr.2011.0019.
    1. Bloomer RJ, Harvey IC, Farney TM, Bell ZW, Canale RE. Effects of 1,3-dimethylamylamine and caffeine alone or in combination on heart rate and blood pressure in healthy men and women. Phys Sportsmed. 2011;39(3):111–120. doi: 10.3810/psm.2011.09.1927.
    1. Farney TM, McCarthy CG, Canale RE, Alleman RJ, Bloomer RJ. Hemodynamic and hematologic profile of healthy adults ingesting dietary supplements containing 1,3-dimethylamylamine and caffeine. Nutr Metab Insights. 2012;5:1–12.
    1. McCarthy CG, Farney TM, Canale RE, Alleman RJ, Bloomer RJ. A finished dietary supplement stimulates lipolysis and metabolic rate in young men and women. Nutr Metab Insights. 2012;5:23–24.
    1. McCarthy CG, Canale RE, Alleman RJ, Reed JP, Bloomer RJ. Biochemical and anthropometric effects of a weight loss dietary supplement in healthy men and women. Nutr Metab Insights. 2012;5:1–14.
    1. Whitehead PN, Schilling BK, Farney TM, Bloomer RJ. Impact of a dietary supplement containing 1,3-dimethylamylamine on blood pressure and bloodborne markers of health: a 10-week intervention study. Nutr Metab Insights. 2012;5:33–34.
    1. Venhuis BJ, de Kaste D. Scientific opinion on the regulatory status of 1,3-dimethylamylamine (DMAA) Eur J Food Res Rev. 2012;2:93–100.
    1. Perrenoud L, Saugy M, Soudan C. Detection in urine of 4-methyl-2-hexaneamine, a doping agent. J Chromatogr B. 2009;877:3767–3770. doi: 10.1016/j.jchromb.2009.09.013.
    1. Vorce SP, Holler JM, Cawrse BM, Magluilo J. Dimethylamylamine: a drug causing positive immunoassay results for amphetamines. J Anal Toxicol. 2011;35(3):183–187. doi: 10.1093/anatox/35.3.183.
    1. A new view of statistics;a scale of magnitudes for effect statistics. .
    1. Csajka C, Haller CA, Benowitz NL, Verotta D. Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects. Br J Clin Pharmacol. 2005;59(3):335–345. doi: 10.1111/j.1365-2125.2005.02254.x.
    1. Stars and Stripes reports: Army study on DMAA will continue. [ ]

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe