Im not particularly up to date on what was finally concluded about the 5-ht2b action on MPH and if it really did have potential for heart valve damage. The two dopamine agonists permax and cabergoline were withdrawn because they could damage cardiac valves with the same mechanism (ie 5-ht2b agonism).

This may be controversial on this board but i really dont want to dive head first into study abstraction land and come up with "we dont know". I assume someone knows what the conclusion was.

Hmm . . . I wasn't aware of this issue re heart valve damage. As far as I know, methylphenidate is a reuptake inhibitor without much in the way of affinity for individual receptor subtypes, so in theory at least, there shouldn't be much of an issue. (At least for direct agonist effects). . . I think the dopamine receptor agonists, due to their inherent structure are more likely to be an issue (they bind directly to the receptor site, not the reuptake site like methylphenidate).

oh, im even less up to date, how does it damage a heart valve ? if it acts on the heart I assumed it meant at worst it pumped harder or faster, does this make it damage the valve ? im being tried on quite a high dose of ritalin for titration purposes but over a short period. seems i find more and more to find out about each day lol sigh ...

A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study.

<!-- google_ad_section_end --> by: JS Markowitz (http://www.citeulike.org/user/Tominator/author/Markowitz), CL DeVane (http://www.citeulike.org/user/Tominator/author/DeVane), LK Pestreich (http://www.citeulike.org/user/Tominator/author/Pestreich), KS Patrick (http://www.citeulike.org/user/Tominator/author/Patrick), R Muniz (http://www.citeulike.org/user/Tominator/author/Muniz)
Journal of child and adolescent psychopharmacology, Vol. 16, No. 6. (December 2006), pp. 687-698.


dl-Methylphenidate (MPH) has been widely used to treat attention-deficit/hyperactivity disorder (ADHD) for the last half century. It had been exclusively available in the racemic form, i.e., a 50:50 mixture of d- and l-isomers. However, a single enantiomer formulation, d-MPH (dexmethylphenidate), became available for general clinical use in 2002. For this reason, the intrinsic pharmacological differences in the effects of d- and l-MPH have recently come under intense investigation. The primary therapeutic effects of MPH are generally recognized to reside in the d-isomer. The present investigation provides quantitative values for a broad range of receptor-level interactions of the individual MPH isomers to better characterize the distinction between dl-MPH versus d-MPH versus l-MPH as it relates to binding affinity at sites associated with relevant central nervous system (CNS) pharmacology, as well as peripheral physiology. Overall, there were few differences in binding affinities between d-MPH and the racemate whereas there were more apparent differences between d-MPH and l-MPH. d-MPH exhibited prominent affinity at the norepinephrine transporter (NET) site, even exceeding such affinity at the dopamine transporter (DAT). These results further demonstrate that affinity for catecholaminergic sites largely resides in the d-MPH isomer. Although binding affinity was not demonstrable at the serotonin (5-HT) transporter site (SERT), novel findings of the study included affinity for the 5-HT1A and 5-HT2B receptor sites for both d- and l-MPH, with d-MPH exerting by far the most predominant effects at these sites. Thus, the emerging data of favorable therapeutic effects of ADHD treatment with d-MPH (and dl-MPH) may be underpinned by affinity and potential pharmacologic effects at NET and DAT sites, as well as sites relevant to serotonergic neurotransmission that may modulate mood, cognition, and motor behavior. However, the present exploratory studies reflect receptor binding affinities only. The specific pharmacological activities (i.e., agonism vs. antagonism) of these compounds await further exploration.

With this we at least know there is some sort of activity at the site in question.

Thanks, now I see where you're coming from.

It's always difficult to extrapolate from binding assays done in vitro to what happens in a living organism.

Often times the concentrations of drugs used are much higher than what would be present in plasma or brain, so you will see all binding, including that which only occurs with very high concentrations of drugs.

I'm not sure that the concentrations here are that high, but it is something to keep in mind when reading these findings. Indeed, the researchers caution that their results must be followed up with more studies, including whole animal.