Oilahuasca Activation Sequence A

SEQUENCE A

The 3 end alkaloid metabolites in Sequence A are proven to be created in vivo in animals. Steps 1-3 are also proven steps. How we get from step 3 to step 4 is currently unknown.

SEQUENCE A - STEP 1: ORAL INGESTION (OR TOPICAL APPLICATION)

Elemicin is ingested orally (or applied topically to the skin).
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SEQUENCE A - STEP 2: CONVERSION TO AN ALCOHOL

Some elemicin is 1'-hydroxylated to the alcohol 1'-hydroxyelemicin. For most allylbenzenes this is performed by CYP2A6, CYP2C9 and CYP2E1, and sometimes CYP1A2.
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SEQUENCE A - STEP 3: CONVERSION TO A PHENYL VINYL KETONE

1'-hydroxy-elemicin is oxidized to the phenyl vinyl ketone 1'-Oxoelemicin by 17bHSD2.
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SEQUENCE A - STEP 4: CONVERSION TO ALKALOIDS

The alkaloids that form in this section have been detected in vivo. But how exactly they form from 1'-oxoelemicin is unknown. A transaminase enzyme may be required, or 1'-oxoelemicin might condense spontaneously to form alkaloids.

1'-Oxoelemicin may condense with available dimethylamine to form the alkaloid adduct 1'-oxoelemicin-DMA, also known as 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)propan-1-one.
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1'-Oxoelemicin may condense with available piperidine to form the alkaloid 3-piperidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one.
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1'-Oxoelemicin may condense with available pyrrolidine pyrrolidine to form the alkaloid 3-pyrrolidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one.
Elemicin-pyrrolidine-metabolite.gif

Of the possible alkaloid metabolites, the dimethylamine form has the lowest lipid solubility and the piperidine form has the highest lipid solubility. Therefore, the piperidine alkaloid form will more easily cross the blood brain barrier.

Of the possible alkaloid metabolites, the dimethylamine form is the most likely to be vulnerable to attack by MAO-A or MAO-B enzymes. Dimethylamines are often primary substrates of MAO. For example N,N-dimethyltryptamine and N,N-dimethyl-4-hydroxyphenylethylamine (hordenine) are primary substrates of MAO.

At this time it is not known which of the possible alkaloid metabolites might be the main active metabolite for each of the allylbenzenes. Other amines may also form.

It’s important to note that in the case of the allylbenzene myristicin, piperidine and pyrrolidine metabolites have been detected but dimethylamine metabolites have not. This indicates that the dimethylamine metabolites might possibly be more vulnerable to attack by enzymes such as MAO-A, MAO-B, etc., leading to their complete destruction prior to being excreted in urine.

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