racemic and/or dextromethylphenidate effect on 5-ht1a receptor

[allthegoodjwh's]

read on wikipedia:

"Methylphenidate has both DAT and NET binding affinity, with the dextromethylphenidate enantiomers displaying a prominent affinity for the norepinephrine transporter. Both the dextro- and levorotary enantiomers displayed receptor affinity for the serotonergic 5HT1A and 5HT2B subtypes, though direct binding to the serotonin transporter was not observed"

actual study here: http://online.liebertpub.com/doi/abs/10.1089/cap.2006.16.687


wondering how it acts on 5-ht1a
if not a direct agonist then how exactly does it modulate activity

also would this explain the more mdma/amphetamine esque effects of empathy and other sertonergic effects as it seems a lot more full than other ndris out there or this could just be placebo but i noticed this even before reading whats posted above
im sure somebody can answer this lol

 

[JackiesBabyy]

I've never heard of methylphenidate giving empathy effects. D-amphetamine and meth can when you have no tolerance but they're known serotonin releasers, not receptor agonists.

 

[sekio]

If methylphenidate has actions at 5ht1a they are comparatively nonexistient/very weak when you look at the stimulant effects.

This study never found if it was an agonist, antagonist, or what. All they found is that MPH binds to a few serotonin receptors.

 

[AlphaMethylPhenyl]

http://www.sciencemag.org/content/283/5400/397.short

http://jpet.aspetjournals.org/content/291/1/19.short

 

[allthegoodjwh's]

interesting this is why i ask and i only start new threads when i cannot find a pre existing answer i am adhd and find that stimulants have a calming effect and dextrophetamine is a great anxiolytic in my opinion and while they say it has mild to no action on seratonin although that coild be different at recreational doses it has like 1/4 se to ne release ratio i believe but anyways its the point that it deffinsoftly feeks loke somethkng else is "there" so to speak a much greater mood elevation and genral enjoyment whih ibdi not get fron methylphenidate at any dose at all.... it just makes me think so hard i ovrrthink life itself and that never ends well in fact ive actually gotten very depressed on it many times which isbodd as irs supposed to be a potent dri... mood elevation. i believe seratonin deffinatly plays a role i a stimulants "useability" or value jlive seen plenty l

 

[NeuroPsyence]

Does anyone with access to the full text of the study want to take an quick look for what the Ki values for 5-HT1a and 5-HT2b binding actually were?

 

[sekio]

It's open access, anyone can view it.

 

[wreckhead]

It's open access, anyone can view it.

Given the 5-HT2B activity, do you think we should be concerned about fenfluramine-like heart disease with long term use? Or is it too weak, like you said. I take 36mg methylphenidate per day in extended release...

 

[sekio]

I wouldn't be suprised if that were the case.

 

[endotropic]

Given the 5-HT2B activity, do you think we should be concerned about fenfluramine-like heart disease with long term use? Or is it too weak, like you said. I take 36mg methylphenidate per day in extended release...

It appears that MPH is acting as an antagonist at the 5-HT2b receptor.
http://www.ncbi.nlm.nih.gov/pubmed/19322953

You'd think with how long ritalin has been around, and the lengthy periods people are prescribed it, someone would have noticed valvulopathies popping up by now if this were an issue.

 

[MeDieViL]

As an antagonist it wont be an issue, also only direct agonists are problematic (no issue with ssri's for example)

 

[immad]

Afaik 5-HT2a receptor antagonists still cause receptor downregulation (don't ask me why). How is this with 5-HT1a antagonism? Will you get downregulation?

 

[NeuroPsyence]

Afaik 5-HT2a receptor antagonists still cause receptor downregulation (don't ask me why). How is this with 5-HT1a antagonism? Will you get downregulation?

No, 5-HT1a antagonism should cause upregulation. 5-HT2a receptor antagonists cause receptor downregulation through a curious combination of internalization, compartmentalization, and degredation. It is a paradoxical effect that is shared with few other receptors.