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methylphenidate vs dexmethylphenidate (Ritalin vs. Focalin)


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I'm currently taking Vyvanse, and I've heard that straight amphetamine-based stimulants like Adderall and Vyvanse can be stronger stimulants than the methylphenidate class like Ritalin, Concerta (Ritalin XR), and Focalin. I'm considering talking to my doctor about something more mild, and I'm looking at the methylphenidates as an option.

What I know about Adderall and Vyvanse is that there are differences. Even if Vyvanse is just the dextro- enantiomer of the amphetamine molecule. What I also know is that dextroamphetamine (along with lisdexamfetamine) has more of an effect on dopamine than levoamphetamine which is found mixed with dextroamphetamine in Adderall, and levoamphetamine has more of an effect on norepinephrine.

Are there similar differences between methylphenidate and dexmethylphenidate? Where one may effect a certain neurotransmitter more than the other would? I'm curious specifically about pharmacology differences and even the slightest differences in mechanism of action. Curious as to what anyone might have to say here.

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There is literally no functional difference whatsoever between methylphenidate and dexmethylphenidate other than the fact that dexmethylphenidate is exactly twice as potent by weight as methylphenidate (i.e. that 5 mg of dexmethylphenidate = 10 mg of methylphenidate). There is no reason to take dexmethylphenidate instead of methylphenidate.

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12 hours ago, JustNuts said:

There is literally no functional difference whatsoever between methylphenidate and dexmethylphenidate other than the fact that dexmethylphenidate is exactly twice as potent by weight as methylphenidate (i.e. that 5 mg of dexmethylphenidate = 10 mg of methylphenidate). There is no reason to take dexmethylphenidate instead of methylphenidate.

Methylphenidate is broken down into threo- and erythro- metabolites and Focalin is strictly the dextro- isomer of the threo metabolite. I can only imagine that the levo-threo isomer and the erythro- isomers only cause more side effects and must have some pharmacological action of some kind even if it is minimal. I'm wondering if as @Velvet Elvis says this could make Focalin more tolerable.

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10 hours ago, browri said:

Methylphenidate is broken down into threo- and erythro- metabolites and Focalin is strictly the dextro- isomer of the threo metabolite. I can only imagine that the levo-threo isomer and the erythro- isomers only cause more side effects and must have some pharmacological action of some kind even if it is minimal. I'm wondering if as @Velvet Elvis says this could make Focalin more tolerable.

This is glaringly incorrect.

  1. threo- and erythro- are diastereomers of methylphenidate, not metabolites of methylphenidate. The primary metabolite of methylphenidate is ritalinic acid, which is pharmacologically inactive.
  2. Racemic methylphenidate is a 50/50 mix of d-threo-methylphenidate and l-threo-methylphenidate (so it's dl-threo-methylphenidate, or d,l-threo-methylphenidate). The erythro- diastereomers are never used in modern formulations of methylphenidate due to being pressor amines that do not have useful clinical effects.
  3. Clinical research has proven that dl-threo-methylphenidate is indistinguishable from equivalent doses of d-threo-methylphenidate in its efficacy and tolerability. d-threo-methylphenidate is a classical example of an evergreened drug, in fact one might say that it's literally one of the best possible examples out there of clear-cut evergreening.
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Wow! Thanks for the information @JustNuts! I did some reading after I read through your explanation and it makes a lot more sense now.

So the modern preparations of methylphenidate don't contain the erythro isomers at all? I was under the impression that regular Ritalin actually contained both.

Had my pdoc appt today and he's starting me on 20mg of Focalin. Pharmacy doesn't have it so I won't actually get to start it until Saturday, but no biggie there.

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Day 3 on Focalin and I have to say I still like it. Again, none of the amped, raw energy that you get with Adderall and Vyvanse, just pure focus. I've read on here that sometimes feel hyper-focused and less social on Focalin than on Adderall or Vyvanse and I can see why. I'm not complaining though. I don't feel stressed at the end of my day. It's a smooth roll the whole way and an easy comedown. Definitely think I could use a higher dose but trying to balance that with my anxiety threshold which with Vyvanse is somewhere between 30 and 40mg.

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On 9/14/2017 at 11:35 AM, browri said:

Wow! Thanks for the information @JustNuts! I did some reading after I read through your explanation and it makes a lot more sense now.

So the modern preparations of methylphenidate don't contain the erythro isomers at all? I was under the impression that regular Ritalin actually contained both.

Had my pdoc appt today and he's starting me on 20mg of Focalin. Pharmacy doesn't have it so I won't actually get to start it until Saturday, but no biggie there.

Np.

Yes, there are no erythro- diastereomers in any modern formulation of methylphenidate. Only threo- diastereomers are used. "Regular Ritalin" (i.e. racemic methylphenidate) contains 50% dextro-threo-methylphenidate and 50% levo-threo-methylphenidate. "Focalin" (i.e. dexmethylphenidate) contains 100% dextro-threo-methylphenidate.

9 hours ago, browri said:

Day 3 on Focalin and I have to say I still like it. Again, none of the amped, raw energy that you get with Adderall and Vyvanse, just pure focus. I've read on here that sometimes feel hyper-focused and less social on Focalin than on Adderall or Vyvanse and I can see why. I'm not complaining though. I don't feel stressed at the end of my day. It's a smooth roll the whole way and an easy comedown. Definitely think I could use a higher dose but trying to balance that with my anxiety threshold which with Vyvanse is somewhere between 30 and 40mg.

Good to hear that it's working.

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9 hours ago, browri said:

Day 3 on Focalin and I have to say I still like it. Again, none of the amped, raw energy that you get with Adderall and Vyvanse, just pure focus. I've read on here that sometimes feel hyper-focused and less social on Focalin than on Adderall or Vyvanse and I can see why. I'm not complaining though. I don't feel stressed at the end of my day. It's a smooth roll the whole way and an easy comedown. Definitely think I could use a higher dose but trying to balance that with my anxiety threshold which with Vyvanse is somewhere between 30 and 40mg.

Good to hear it's working well! Is there a reason you went with Focalin instead of Ritalin? I take Ritalin and it has the same effect that you've described - strong pure focus and the extended doesn't make me feel like it's an abrupt comedown.

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I think we just ended up going with Focalin because there was no reason no to. There's always the possibility that an "enantiopure" molecule COULD be more tolerable than the racemic form. I felt that way with Celexa and Lexapro. Both made me fatigued but Celexa was worse. So I don't have Ritalin to compare on effect between the two.

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On 9/19/2017 at 8:16 AM, browri said:

I think we just ended up going with Focalin because there was no reason no to. There's always the possibility that an "enantiopure" molecule COULD be more tolerable than the racemic form. I felt that way with Celexa and Lexapro. Both made me fatigued but Celexa was worse. So I don't have Ritalin to compare on effect between the two.

In the case of citalopram vs escitalopram, the differences in binding profiles / receptor affinities are actually significant enough to matter (especially so for 5-HT2C, H1, and α1). In the case of dexmethylphenidate vs methylphenidate, the differences in binding profiles / receptor affinities are nowhere near significant enough to matter.

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I don't know there do seem to be SLIGHT differences but you're right. Probably nothing to make that big of a difference:

Methylphenidate/Dexmethylphenidate
5-HT IC50 > 10000 nM / >10000 nM
SERT Ki > 10000 nM / >10000 nM
DA IC50 = 20 nm / 23 nM
DA Ki = 121 nM / 161 nM
NET IC50 = 51 nM / 39 nM
NE Ki = 788 nM / 206 nM
5-HT1A IC50 = 5000 nM / 3400 nM
5-HT1A Ki = 10000 nM / 6800 nM
5-HT2B IC50 = >10000 nM / 4700 nM
5-HT2B Ki = >10000 nM / 4900 nM

It would seem that dexmethylphenidate is just BARELY more noradrenergic than its racemic counterpart.

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On 9/23/2017 at 8:26 AM, browri said:

I don't know there do seem to be SLIGHT differences but you're right. Probably nothing to make that big of a difference:

Methylphenidate/Dexmethylphenidate
5-HT IC50 > 10000 nM / >10000 nM
SERT Ki > 10000 nM / >10000 nM
DA IC50 = 20 nm / 23 nM
DA Ki = 121 nM / 161 nM
NET IC50 = 51 nM / 39 nM
NE Ki = 788 nM / 206 nM
5-HT1A IC50 = 5000 nM / 3400 nM
5-HT1A Ki = 10000 nM / 6800 nM
5-HT2B IC50 = >10000 nM / 4700 nM
5-HT2B Ki = >10000 nM / 4900 nM

It would seem that dexmethylphenidate is just BARELY more noradrenergic than its racemic counterpart.

Eh, I'd say the difference is more from measurement uncertainty than anything else given the extremely close quoted IC50 values and the broad range of Ki/IC50 values observed (I've read basically the entirety of the existing literature on the subject and was the one who selected the "representative" values for that table you're citing in the first place!). Like I said previously, this is something that has been tested in actual head-to-head trials, and there were no differences in effects or side effects, so any of the tiny differences in receptor/binding affinities are too subtle to detect in the real world (which is to be expected, given the values observed).

Edited by JustNuts
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  • 4 months later...

This is just anecdotal, but the first time I tried methylphenidate, it was great until my pulse went up to 150 (2.5X normal) or so late in the day. So I haven't been back. Later, I was on Focalin for quite a while without having the problem. For all I know, if I tried regular methylphenidate now, I wouldn't have the problem, though I'm not eager to do so.

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