Focalin and ethylphenidate

[ivoryline]

I know that when ethanol and methylphenidate are consumed together a compound forms in the liver called ethylphenidate, which increases the euphoric properties of methylphenidate. Would the compound ethylphenidate still form in the liver after consumption of ample amounts of ethanol and focalin (dexmethylphenidate)?

 

[pallidamors]

It should still form ethylphenidate, if your information is correct. The "dextro" in dextromethylphenidate just refers to the fact that focalin contains only the right-handed stereoisomer of methylphenidate, whereas regular methylphenidate contains both the right-handed and left-handed isomers in equal amounts (dextromethylphenidate and levomethylphenidate). So, in this case, you'd probably end up with just dextroethylphenidate.

This conversion seems like the cocethylene (sp?) conversion that forms from ethanol and cocaine, but I havent heard of ethylphenidate before. I'll have to read up on it.

Oh, and if you want a better explanation of stereoisomers, google the word "chirality" and you should be able to read up on it. Basically when you're dealing with three-dimensional molecules, you can end up with mirror image drugs which usually have the same effects, but with in some cases, such as with methylphenidate, one of the mirror images is responsible for more of the beneficial or recreational effects.

 

[ivoryline]

This is a great explanation. Thanks. I'll have to look up chirality because i never did understand how the dextro- and levo- business worked.

But does anyone know if dextroethylphenidate is effective at producing the same side effects as ethylphenidate? Does the liver need the levo- "side" also to produce the compound?

 

[pallidamors]

When your liver creates ethylphenidate from methylphenidate, it's actually a 50-50 mixture of dextro- and levo- ethylphenidate that you end up with, I don't think that you'd need both isomers in order for the liver to perform the conversion, though.

I think that dextroethylphenidate would probably feel the same as the dextro/levo mixture of ethylphenidate, possibly even slightly better, since it would be similar to dextromethylphenidate vs. a dextro/levo methylphenidate mixture...and I've always found dextromethylphenidate to be more recreational.

 

[lukw10]

do you guys really get much/any euphoria from taking focalin? I've taken it up to 80mg oral and 20mg snorted (XRs crushed to smithereens). Empty stomach and tried with food, ~8 of sleep two nights before hand, and all i felt was a continuous need to be pill popping every hour to maintain the roller coaster of like minor euphoria --> pretty pretty sad. So the downs didn't feel nearly worth it. Although i do take adderall (not at the same time, i got switched back after 2 days) so maybe some cross tolerance? But usually my addy tolerance is down by that time cos i take 4 days off a time (friday, saturday, sunday, monday) and eat/sleep the whole time.

 

[Riemann Zeta]

Actually, there was a study done a few years ago regarding ethylphenidate formation in humans. After a standardized dose of racemic methylphenidate (good old-fashioned Ritalin), they found that levo-ethylphenidate (the inactive enantiomer) was formed almost exclusively over dex-ethylphenidate. However, I don't know if these results are valid if the (d)-isomer is the only one consumed--perhaps the transesterification enzyme prefers the (l)-isomer, but will work with either.

 

[jonny87]

I find this thread very interesting because I'm sure I noticed some kind of euphoric effect, or at least a positive much more sociable effect when I combine ritalin with alcohol compared to either of them on their own. In fact I stopped taking my ritalin during the daytime because I didnt like the effects of it (just took it on nights out).

However, from doing a bit of research which I'v written below, it seems impossible that ethylphenidate would have any noticable effects at all.

Actually, there was a study done a few years ago regarding ethylphenidate formation in humans. After a standardized dose of racemic methylphenidate (good old-fashioned Ritalin), they found that levo-ethylphenidate (the inactive enantiomer) was formed almost exclusively over dex-ethylphenidate.

I'm not sure if I found the same study that you read or not, but I did find this:

"Ethanol after or before MPH significantly (P<0.0001) elevated the geometric mean for the maximum d-MPH plasma concentration (C(max) (+/-SD)) from 15.3 (3.37) ng/ml to 21.5 (6.81) and 21.4 (4.86), respectively, ...

...The metabolite l-ethylphenidate frequently exceeded 1 ng/ml in plasma, whereas d-ethylphenidate was detected only in low pg/ml concentrations. "

So, the active d-MPH has a concentration in the blood of about 15 or 21 ng/ml depending on which order the ethanol and methylphenidate were consumed. But the active d-ethylphenidate only has a concentration of "low pg/ml concentraions."

1 ng=1000 pg so if "low pg/ml concentrions" means say 20 pg/ml then the concentration of active d-ethylphenidate is 1000 times less than that of active d-MPH!

Not only that but another study states that "d and DL-methylphenidate and ethylphenidate exhibited comparably potent low inhibition of the dopamine transporter, whereas ethylphenidate was a less potent norepinephrine transporter inhibitor.." which results in a "...reduced stimulatory effect of d-ethylphenidate relative to d-methylphenidate"

So not only is the concentration of the active d-ethylphenidate much less than d-MPH, but the d-MPH is a stronger stimulant than d-ethylphenidate too!

So overall, am I right in thinking that there would be no noticeable effects from the ethylphenidate which is formed when drinking alcohol with methylphenidate?

If that's true then where did the synergistic effects some from when ritalin and is taken with alcohol?

Jonny

 

[Solide]

If that's true then where did the synergistic effects some from when ritalin and is taken with alcohol?

1) they found that levo-ethylphenidate (the inactive enantiomer) was formed almost exclusively over dex-ethylphenidate

2) Ethanol after or before MPH significantly (P<0.0001) elevated the geometric mean for the maximum d-MPH plasma concentration

3) ethylphenidate was a less potent norepinephrine transporter inhibitor

I'm guessing it goes sort of like this:

1) Since only levo-ethylphenidate is produced I'm guessing this is done by transesterification of l-MPH, hereby reducing l-MPH concentrations and thus a larger d-MPH:l-MPH ratio is created. And we know d-MPH > l-MPH so this would automaticaly give better subjective feelings.

2) If this is done by hepatic metabolism it wouldn't be unlikely that the BA of MPH is raised (because your liver is 'busy') though I'm just guessing here and could be off completely. But in case this is true, and the study does say d-MPH plasma concentrations were raised, this would be potentation.

3) Since ethylphenidate is less potent than methylphenidate (and L-ethylphenidate apparantly even inactive) its effects wouldn't "interfere" with the MPH effects thus letting you feel the euphoria of d-MPH even more now it's not clouded with shitty NRI-action from l-MPH

Also, there is probably some sort of 'speedball' effect from the ethanol too.

 

[jonny87]

3) Since ethylphenidate is less potent than methylphenidate (and L-ethylphenidate apparantly even inactive) its effects wouldn't "interfere" with the MPH effects thus letting you feel the euphoria of d-MPH even more now it's not clouded with shitty NRI-action from l-MPH

I think that l-MPH has no action at all or very little action from the statements I have written below from studies. But it does partially block the d-MPH from working it seems:


"...the l-isomers of both methylphenidate and ethylphenidate were biologically inactive."

"...animal and human studies have confirmed that the d-MPH isomer is responsible for the pharmacodynamic effect of MPH."

"The behavioral effects of the enantiomers of MPH have been tested in several animal models, and results indicate these observed behavioral changes are likewise mediated by d-MPH, whereas l-MPH has little or no effect...

...behavioral studies conducted in rats demonstrate an attenuation of the effect of d-MPH in animals pretreated with l-MPH, suggesting that l-MPH may interfere with the action of the active enantiomer"


So it seems that l-MPH has little or no effect itself other that stopping the d-MPH from working properly.

So effectively, consuming alcohol with ritalin would be the same as increasing the dose of ritalin, due to the effects 1 and 2 that you mentioned and also that there would be less l-MPH to block the action of the d-MPH.

Or perhaps more accurately it would be more like taking focalin due there being so little l-MPH in the blood compared to d-MPH (see below)?

"l-MPH was present in plasma only at 1-3% of the concentration of d-MPH, except in the poor metabolizer where l-MPH exceeded that of d-MPH."


Does this sound right based on the evidence?

If so then shouldn't the effects of when ritalin and alcohol are consumed together be the same as taking focalin?

Jonny

 

[Solide]

Hm, i've never tried Focalin (not available here) but I always thought it felt subjectively different than Ritalin (smoother) and not just 'stronger', so I assumed that l-MPH had an effect of it's own rather than just blocking d-MPH effect.

You know more about this than me though I can't really speculate any further about the pharmacology.

The only thing I can come up with is the speedball effect where alcohol takes the rough edges of off MPH and MPH provides euphoria and a little clarity to the alcohol-buzz.

 

[jonny87]

Hm, i've never tried Focalin (not available here) but I always thought it felt subjectively different than Ritalin (smoother) and not just 'stronger', so I assumed that l-MPH had an effect of it's own rather than just blocking d-MPH effect.

Yes I thought this too. The last quote in my previous post used behavioural studies to test the effect of the different isomers of MPH. Is it possible then that the l-isomer of MPH doesnt affect BEHAVIOUR like the d-isomer does, but still causes the person/animal to feel a bit groggy/shitty/weird due to periphery effects? The scientists wouldnt be able to detect these periphery effects if they didnt effect behaviour, and since it is an animal study there was no way to ask the participants how they felt.

So perhaps the l-MPH partially blocks the d-MPH, but also adds to the side effects (as long as these side effects dont effect behaviour).

This would explain why ritalin during the day made me feel weird, zombie like, slightly moody, and groggy, whereas as with alcohol (making the l-MPH much lower in concentration and the d-MPH higher) I felt energized, sociable and in a great mood. Again, by the looks of the studies it seems that the ethylphenidate produces is too little to do anything.


This makes me wonder whether focalin would feel more like taking ritalin with alcohol (not enough alcohol to feel any drunken effects). ie. more euphoric and sociable without horrible side effects that ritalin.

does anyone have any experience with taking ritalin + alcohol and taking focalin? How do they compare?

 

[Emericana]

Yes I thought this too. The last quote in my previous post used behavioural studies to test the effect of the different isomers of MPH. Is it possible then that the l-isomer of MPH doesnt affect BEHAVIOUR like the d-isomer does, but still causes the person/animal to feel a bit groggy/shitty/weird due to periphery effects? The scientists wouldnt be able to detect these periphery effects if they didnt effect behaviour, and since it is an animal study there was no way to ask the participants how they felt.

So perhaps the l-MPH partially blocks the d-MPH, but also adds to the side effects (as long as these side effects dont effect behaviour).

This would explain why ritalin during the day made me feel weird, zombie like, slightly moody, and groggy, whereas as with alcohol (making the l-MPH much lower in concentration and the d-MPH higher) I felt energized, sociable and in a great mood. Again, by the looks of the studies it seems that the ethylphenidate produces is too little to do anything.


This makes me wonder whether focalin would feel more like taking ritalin with alcohol (not enough alcohol to feel any drunken effects). ie. more euphoric and sociable without horrible side effects that ritalin.

does anyone have any experience with taking ritalin + alcohol and taking focalin? How do they compare?

I honestly couldnt tell the difference.

have done ritalin many times. maybe ritalin felt smoother than focalin.

i have only experience with snorted focalin... dont exactly remember how much i did because it was a few year back.... was a bunch tho. must have been 30-40mg? I remember doing a lot of lines.

was very drunk, verrrry stimulated... and ungodly horny. but i couldnt get it up. funny how that works.