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Misc Brief hypertensive crisis with Adrafinil and Selegiline (Deprenyl): The order matters

SweetSisterRay

Greenlighter
Joined
Oct 18, 2011
Messages
2
Just wanted to pass on a warning to those who might mix Adrafinil and Selegiline

3 days ago a friend of a friend (~25y/o male, healthy) woke up pretty sleepy from a long night of studying with only a couple hours sleep.
Under normal circumstances this would pose no problem to them as coffee and the adrafinil they had legally obtained would erase most of the tired residue and allow them to function properly.
However for three days prior they had been field testing low dose selegiline at 3mg/day sublingually for general improvement in mood, motivation and anti-aging effects. They had also read anecdotal reports of combining modafinil with selegiline on imminst and determined that as long as the dosges were low there would be low chance of an adverse reaction/
Upon waking they took approximately half of a 300mg Adrafinil (150mg) and made coffee like any other extra tired morning.
Prior to leaving the house they ingested their 3 daily drops (3mg) of sublingual Deprenyl and left to catch the bus.

Within less than 2 minutes their pulse shot up frighteningly to approximately 230 beats per minute as measured by the stopwatch on their cell phone but blood pressure seemed fine and no significant impairment in mental activities were observed. For the next three minutes panic began to mount as the heart rate would not subside and even slightly increased. They began to seriously consider walking back to the house or calling 911 if symptoms worsened any further and quickly scrawled a message on his laptop detailing the dosages should he be found unconscious at the bus stop. Upon boarding the bus ~10 min post deprenyl ingestion, pulse was approximately 190 but showed signs of improving. At 30min heart rate had stabilized to approx 160 and by 1 hour heart rate was below 100.

At + 6hr an additional 75 mg of adrafinil was taken
At + 7hr slight headache was noted but no rise in blood pressure
At + 7.5 hr an additional 75 mg of adrafinil was taken with another cup of coffee
Slight side effects (headache) with moderately more intensity than standard adrafinil were noted from this point out but no increase in heart rate

Why then when taken later in the day did the adrafinil not create the same hypertensive crisis as before?

1. The order of addition matters
2. Adrafinil ingestion induces expression of liver enzymes which catalyze its metabolism and excretion


Analysis:
At dosages less than 5mg/day Selegiline retains selectivity for MAO-B isoform and does not inhibit MAO-A responsible for many of the nasty side effects of other monoamine oxidase inhibitors.
Moreover since dosing had only been done for three days prior it is unlikely that full saturation of MAOB had been achieved as they were able to drink alcohol and eat cheese with no problems the day prior.

Their interpretation is this: Adrafinil and Modafinil acts in the central nervous system as well as the peripheral nervous system to influence the level of monoamines either through reuptake inhibition, vesicle formation or other means but the effect is the same. The adrafinil at the time of deprenyl ingestion had already been metabolized into modafinil as the effects were already noticeable. Deprenyl when free in the body due to its similar structure to amphetamine can act as a dopamine norepinephrine releasing agent. Ingestion of the deprenyl triggered a release in the monoamines that were already activated before it had a chance to irreversibly bind MAOB. Upon binding MAOB the deprenyl was no longer available to pass through the blood and act as a peripheral monoamine releasing agent and so as it bound the sympathetic effects became diminished due to reduced plasma concentration. In short the adrafinil in the peripheral potentiated the deprenyl in the peripheral before it irreversibly bound to MAOB in the CNS

Administration of adrafinil later in the day produced no cardiovascular effect for a similar reason. At this time total Deprenyl in the body was still probably very high due to its long half life

Alternatively one could argue that it was because of adrafinils known mechanism of inducing liver enzymes that catalyze adrafinils metabolism. AFOAF does not believe this because the 150mg taken later in the day was just as effective as the equivalent dosage taken earlier in the day

Hope this helps someone
 
With all due respect, this was a panic attack - it seems very clear.

Adrafinil has to be metabolized into modafinil, which then takes a little while to have it's effect. I will agree that there was already MAO-B inhibition from the previous two days, but to what extent, we can't postulate.

Caffeine + MAO-BI may have exacerbated an underlying condition. These symptoms coincided with dosing, not absorption.

Caution is a good idea with any combination, but I think it would be helpful to clarify what is and isn't a side effect of a given anecdote.

edit: I know I necro'd this thread but I found it when looking through selegiline threads so I figure other people will hit it too. Avoiding misinformation. Hopefully others will comment on their experience with selegiline and ardr/modafinil.
 
I would like state with with full certainty that this was not a panic attack, to avoid casual dismissal of this combination as safe.

This incident was also not a function of coffee and selegiline as that combination at those dosage levels has since been tried on numerous occasions without incident.

The real kicker as to why this was acutely cardiotoxic is probably due to the difference in bioavailability of the different forms of selegiline. AFOAF had been under the erroneous impression that 1mg of selegiline sublingual is the same as 1mg taken orally - when really 1mg sublingual is approx 5mg orally. If 10 mg orally is enough to maximally inhibit MAO-B then 3 drops = 3mg sub = about 15mg orally which is enough to start going for MAO-A as well. Be very careful with different forms of selegiline, the tabs will have different effects from the drops. Had this been known at the time a very unpleasant experience could have been avoided. I want to stress that this was not a panic attack and a very real adverse drug reaction when taken under those circumstances. Heart rates don't just spike to 230 when you're walking up the street to the bus like you do every other day.

be careful guys!

as a note (nuvigil 75mg) /(selegiline 1mg sublingual) was found to be quite nice but caution would be advised with higher doses or any combination thereof.
 
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