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stimulus potentiation via deprenyl (selegeline)

ebola?

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stimulant potentiation via deprenyl (selegeline)

First off, I want to consider this hypothetically, as I'm pretty sure that these combos are dangerous.

My layperson speculation about what's going on:

At doses where deprenyl is entirely selective for MAOB, you first might have direct potentiation, as MAOB is responsible for the metabolism of phenethylamine derived drugs. Second, you would have increased effective dopaminergic release, as MAOB is prevented from catabolizing dopamine. Depending on the time-course of MAOB's action, you'd have potentiation of immediate stimulant effects and/or increased duration. Anyone know which of these we'd expect? Third, you'd have reduced neurotoxicity, as deprenyl would prevent MAOB from catabolizing dopamine, which would release various free-radicals. Finally, you'd have possibly dangerous increased temperature, pulse, and BP when deprenyl prevents the breakdown of dopamine in the non-brain body. This effect could exacerbate neurotoxicity.

ebola
 
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I think he's wondering moreso about the pharmacodynamics of selegeline's MAOB properties along with amphetamine.

Amphetamine inhibits MAO-A to increase NE/DA levels, along with a reverse pump (amphetamine-modulated dopaminergic release) action that even potentiates the current MAO inhibition.

I would be weary of even MAOB inhibitors. Monoamines are already drastically increased from amphetamine; including another (similar phenethylamine) MAO inhibitor into the mixture is asking for trouble as you stated.
 
well, i could dig up my early redtinged warnings and dont-do-its, but i guess damage has been done and so...
 
fastandbulbous said:
Selegeline & cental stimulants runs the risk of a nasty case of hyperthermia (which can end up with a trip to A&E, especially in warm summer conditions) unless you know what you are doing and are very careful


The hypertension seems like the bigger concern for most people. High HR and very high BP = MI far too often.
 
Selegiline by itself upped my blood pressure and reduced blood flow to my extremities in a way that I have not seen stimulants do before.

I am guessing this is because there was far more dopamine to convert to epinephrine?
 
>>
Amphetamine inhibits MAO-A to increase NE/DA levels, along with a reverse pump (amphetamine-modulated dopaminergic release) action that even potentiates the current MAO inhibition.>>

Interesting. So wait a minute. Would this entail that amphetamines would potentiate tryptamine psychedelics a la p. harmala?
...
And I'm being quite literal when I say that I want to explore the issue hypothetically....no SWIM shit here. :)

ebola
 
It's controversial as a harm reduction tool, but I know of several people taking selegiline with MDMA or meth and coming out okay. The only thing is that you must be very careful with your dose.

We won't really know how safe it is until someone decides to do a proper study on the polypharmacy of the drug.
 
this won't matter for me for a long time, if ever...
...but would a good tester dose be like 25 percent of the usual dose?

ebola
 
No real safe dose has been established... Best to probably run it up the Shulgin route and start with a miniscule dose and continue doubling until you reach activity (not all in one session!), all whilst monitoring body temperature and blood pressure.
 
there is a journal infact on pubmed that says SELEGILINE is SAFE with METHAMPHETAMINE. infact, selegiline does not increase blood pressure or heartrate when taken with meth.
 
Advanc3d said:
there is a journal infact on pubmed that says SELEGILINE is SAFE with METHAMPHETAMINE. infact, selegiline does not increase blood pressure or heartrate when taken with meth.
Link?

Source: DailyMed

As with other MAOIs, Selegiline is contraindicated for use with sympathomimetic amines, including amphetamines as well as cold products and weight-reducing preparations that contain vasoconstrictors (e.g., pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine).
 
Well, it was an article that referred to methamphetamine administration in squirrel monkeys and yes, it apparently was safe for them and none of them died.

Reduced cardiovascular effects of methamphetamine following treatment with selegiline .
Selegiline is a specific MAO-B inhibitor. As MAO-B has been shown to be significantly involved in the metabolism of dopamine in certain regions of the primate brain, selegiline has been proposed for use in the treatment of drug addiction. Selegiline is also metabolized in vivo to l-methamphetamine. Therefore, when given in combination with psychostimulants such as d-methamphetamine, there is the potential for adverse effects. To study this possibility, squirrel monkeys were treated with chronic selegiline and tested with two doses of d-methamphetamine (0.1 and 1.0 mg/kg, i.v.). Following at least 7 days of treatment with once daily 0.3 mg/kg i.m. selegiline, the effects of methamphetamine on blood pressure and heart rate were no different than the effects of methamphetamine observed prior to selegiline treatment. However, following at least 10 days of treatment with 1.0 mg/kg i.m. selegiline, the effects of methamphetamine on blood pressure and heart rate were significantly reduced. Both methamphetamine and amphetamine were detected in plasma following chronic selegiline treatment. When monkeys were given an acute selegiline injection prior to methamphetamine, reduced cardiovascular effects were also seen. These results indicate that selegiline can be used safely even in combination with methamphetamine, as the cardiovascular effects of the drug combination were no greater than either drug alone, and were actually reduced at the higher selegiline dose.
http://linkinghub.elsevier.com/retrieve/pii/S0376871603001972

I believe most of the contraindication is grandfathered from non-specific MAOIs, and I'm not sure the interaction between MAO-B inhibitors and amphetamines has been extensively tested in humans.

The following is a free full text paper from Nature on selegiline, dopamine, and amphetamine attenuation in rats: http://www.nature.com/bjp/journal/v126/n4/full/0702389a.html
 
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