TCAs

[arctica]

what do you think mdma's effect on 5htb2 is ? partial agonist, full agonist, very selective ? because when i took it regularly i developed heart problems.

Out of curiosity, what kind of heart problems? QT prolongation? Valve disease? Tachycardia?

 

[asecin]

arctica, no idea the name for it. i just started having horrible chest pains even after i stopped mdma for a week or so. just painful pressure dunno what it is.

 

[sekio]

MDMA is a 5ht2b full agonist I think, but it is not totally selective for 2b.

See also: http://www.ncbi.nlm.nih.gov/pubmed/18337424

Perosnally I think it is unlikely your "heart problems" can be ascribed to 5ht2b agonism alone. Esp. if it is a classical panic- or stimulant- type "problem" like elevated heart rate, palpitations, or such. Especially if it is an acute attack in response to dosing a drug; and it is caused by medication not particularly selective for 5ht2b.

I would be more likely to blame it on NE reuptake inhibiton or adrenergic agonism. NE is a known regulator of cardiac output and sudden rises in postsynaptic NE leves can make people panic, or at the very least feel uncomfortable. Many A/D's as well as MDMA produce part of their effect by blocking NE reuptake.

 

[ebola?]

i just started having horrible chest pains even after i stopped mdma for a week or so.

This is a bit unclear...were you using mdma more than weekly, taking a week long break following this...or are you just saying that the unpleasant effects from sporadic use extended a week or more?

If the case is the former...well, you should expect all kinds of shitty after-effects.

MDMA is a 5ht2b full agonist I think, but it is not totally selective for 2b.

Right, but I thought that MDMA's affinity at other 5ht sites was weak enough to be functionally negligible (though I should dig up additional studies, since reported affinity and efficacy can vary so wildly by experimental methodology employed).

I would be more likely to blame it on NE reuptake inhibiton or adrenergic agonism.

And obviously, MDMA is a strong NE releaser...why would we focus on reuptake inhibition instead? Same implications though...and MDMA indeed is significantly directly agonistic at a couple adrenal receptors.

ebola

 

[sekio]

*NE release or reuptake inhibition, sorry.

I do recall MDMA has some affinity for 5ht1a as well. Perhaps 5ht2c and a few others. Its affinity for serotonin release is much higher than its binding effects at postsynaptic 5htrs though, IIRC.

 

[ebola?]

I do recall MDMA has some affinity for 5ht1a as well. Perhaps 5ht2c and a few others.

The "Psychedelics and the Human Receptorome" article found no significant activity at either of these sites, but...I think I'd need to see some corroborating research to truly believe it.

ebola

 

[sekio]

Maybe it's related to downstream activation by 5ht release, then... see this article for evidence of 5ht1a's involvement in oxytocin release and this for some evidence of 5ht2a/b/c involvement in other f/x as well. This for evidence that 5ht2c is involved in the pro-anorexic effects.

Also, do broad-spectrum 5ht antagonists (not neccesarily binding to SERT) not reduce the f/x of MDMA?

 

[endotropic]

Maybe it's related to downstream activation by 5ht release, then... see this article for evidence of 5ht1a's involvement in oxytocin release and this for some evidence of 5ht2a/b/c involvement in other f/x as well. This for evidence that 5ht2c is involved in the pro-anorexic effects.

Also, do broad-spectrum 5ht antagonists (not neccesarily binding to SERT) not reduce the f/x of MDMA?

All of those effects could be secondary to increased 5-HT release leading to increased activation of those postsynaptic receptors. Direct binding of MDMA to those postsynaptic receptors doesn't have to be involved.

Anyways to the OP's questions about his chest pains, I seem to remember that you currently, or previously abused cocaine quite heavily. Maybe your history is just catching up to you.

 

[MrSquishy]

Hey all, first time post here, longish lurker (on and off). Anecdotally, FWIW, etc. I have found clomipramine to be very helpful for me w/r/t depression and OCD. I'm busy and can't go into too much detail, but over the past 9 years I've had legitimate (i.e. 8 weeks minimum) on 8 different AD's (including the all-mighty and dirty-as-hell tranylcypromine). A combination of 225mg venlefaxine + 30mg mirtzapine gave me a solid 6 months of remission. Currently, Clomipramine is helping immensely and is providing me with enough stability of mood that I've actually been taking courses at community college! Which, come on, at age 27 feels so terrible, but it's a hell of a lot better to be taking a course or two while working a dead-end job than to be working a dead-end job and not doing anything else at all.

To mitigate the side effects (crazy sweating and consitpation) I take 250 mg citicoline b.i.d. Regular choline sourced from lecithin did nothing nor did 300mg "alpha gpc choline" b.i.d. - I'm also fully aware that the anti-cholinergic side-effects may have subsided on their own as I have been on the clomipramine for 5 months, which would make the citicoline nothing more than an expensive placebo.

There also aren't any dietary restictions on any TCA (and I have OCD as well, so I would know if there were any interactions). The main deterrent to their use (other than the whole practice of psychiatry going to hell in this country through the insurance companies making any legitimate psychiatric treatment near impossible...) is that it is much easier to O.D. w/ tricyclics and older MAOI's than with the "newer" ssri's and snri's.

I also think that many psychiatrists are not comfortable prescribing them. It's only since I have been going to a university psych center that clomipramine was brought up. It's been similar with my partner - she's finding success with nortriptyline after disastrous trials of with sertraline and paroxetine (not simultaneously, of course). She's been seeing a psychiatrist who finished up his residency back in the early 80's - right before the whole "prozac revolution" stole the spot light.