Saturday, January 19, 2013

Methoxyoctopamine: Structure & Activity

p-Methoxyoctopamine (Para-Methoxy-Octopamine, P-OMe-Octopamine) is an interesting compound formed after en vivo hydrolysis of various natural amides such as Aegeline and Tembamide.

Structure Activity Relationships (SAR)
According to the marketing advertisements related to both compounds, these compounds are purported to be potent beta-agonists, and therefore suitable for inducing fat loss, as well as promoting "focus," and endowing "CNS stimulation." There is no evidence for any of these claims, although there is decades of SAR research which would contradict these statements.

As has been discussed in many previous articles, methylating the para position removes beta-1 and beta-2 adrenergic affinity. This is one of the ways the body "deactivates" catecholamines with the enzyme Catechol-O-Methyl-Transferase (COMT). Since methoxyoctopamine already possesses a para-methoxy substituent, it is already deactivated. Conversely, a para-methoxy substituent does not remove beta-3 agonism. In mice and other animals, this property may confer significant fat loss potential. Unfortunately, as I mentioned in the previous article, beta-3 agonism does not promote significant fat loss in humans.

CNS Stimulation
P-OMe-Octopamine also possesses a hydroxy (-OH) subsituent on the beta carbon. This substituent effectively eliminates significant CNS penetration, and therefore would remove "CNS stimulation" as a potential effect of the drug. Conversely, the para-methoxy substituent actually promotes BBB penetration, and therefore would allow CNS penetration in the absence of the beta-OH. Unfortunately, the effects of CNS penetration would only be negative (i.e. dysphoria) and so the lack of CNS penetration is probably a good thing (See Para-methoxyamphetamine). 

Since methoxyoctopamine is a primary phenylethylamine, it may still retain properties related to catecholamine releasement (See the Pharmacology of 1,3-DMAA). This effect may allow a transient dumping of synaptic norepinephrine which may manifest as symptoms of the adrenergic cascade (tachycardia, tachypnea, hypertension). In contrast to 1,3-DMAA which probably has significant BBB penetration, methoxyoctopamine would not produce the "positives" of catecholamine releasement such as true CNS stimulation, and focus. The effects produced by methoxyoctopamine would probably be similar to those produced by N-methyltyramine, albeit relatively weaker due to the para-methoxy substituent.

  • Para-Methoxy-Octopamine formed after en vivo hydrolysis of Aegeline and Tembamide.
    • The para-methoxy substituent removes beta-1 and beta-2 adrenergic receptor affinity, although still allowing for the possibility of beta-3 receptor affinity.
      • No ability to induce lipolysis (fat loss) in humans
    • The beta-OH removes substantial CNS penetration.
      • No ability to produce CNS stimulation.
    • May still retain catecholamine releasing potential, allowing for transient peripheral stimulation.
      • Much better alternatives exist.


  1. I am confused as to why you assert Beta-3 Adrenergic Receptor agonism does not induce lipolytic/thermogenic effects in humans. The rather abundant amount of research states otherwise. Please explain.

  2. The receptors exist, but only in low density & low functioning (via receptor DNA polymophisms). They do not signficantly contribute to lipolysis in humans, whereas in other mammals they do (specifically those with higher concentration of BAT). This is one of the reasons why beta3 receptor agonists have failed in clinical trials.

  3. i was looking at the talk about sarcosine, being a glycine activator, and also about your piracetam article. I was wondering if you could investigate into sunifiram? anything peculiar about it? comparisons to BZP? i thought the tembamide also looked similiar as well..