Methadone, a NARI?? and a few more q's

[jasoncrest]

Methadone, a SNRI?? and a few more q's

I have a five questions concerning Methadone:

I read in several places that Methadone is:
-a full mu agonist
-a NMDA antagonist
-a Serotonin & Noradrenaline Reuptake Inhibitor
(here's one source: www.info.gov.hk/aids/harmreduction/workshop2003/pdf/5a-s3-1.pdf , but there are many other...)

#1. Is this Serotonin & Noradrenaline Reuptake Inhibitor activity significant?
I mean, is 100mg a stronger Serotonin & Noradrenaline Reuptake Inhibitor than 37,5mg Venlafaxine?

#2. Is Serotonin & Noradrenaline Reuptake Inhibitor activity of Methadone strong enough to cause a Serotonin Syndrome if someone takes Methadone + Extasy?

#3. I read somewhere that Levo-Methadone was the full mu agonist, and Dextro-Methadone was the Serotonin & Noradrenaline Reuptake Inhibitor; is this true?
(I read that on 1 page, but couldn't find other sites telling the same)

#4. Is the NMDA antagonist activity of Methadone strong enough to give a noticeable effect and to reduce tolerance?
If we consider NMDA antagonism only, how Methadone compares to Ketamine? Can they be compared? What dosage of Methadone gives the same NMDA antagonist effects than 100mg Ketamine?

One more question....

#5. I read in many pages that neuroleptics/anti-psychotics can precipitate withdrawal symptoms in Methadone-addicted patients.
Here are 2 sources, there are many more on google:

http://content.karger.com/ProdukteD...abe=230672&ArtikelNr=83097&filename=83097.pdf

http://www.psychopharmacology.com/p...3klfmpGkC3jBQpsW!588122478!-949856145!8091!-1

What's the mechanism? How can neuroleptics put an opiate-addict in withdrawal?
Neuroleptics don't work on opiate receptors, right?
They are mostly dopamine D2 antagonists...

 

[BilZ0r]

#1. Maybe, the paper I think that shows the affinities is:
http://www.ncbi.nlm.nih.gov/entrez/...st_uids=7562497&query_hl=2&itool=pubmed_Brief
but I can't get it online. Some of the opioids are relatively potent SS/NRIs

#2. MDMA + SSRIs don't cause serotonin syndrome (SSRIs block MDMA). SSRIs + SSRIs cause serotonin syndrome. And yes, some opioids (esp phenylpiperidines) can cause serotonin syndrome when mixed with SSRIs.

#3, no idea.

#4. Probably insignificant. Methadone inhibits NMDA receptors with a Ki in the low micromolar range, about 1000x less than it's mu effect [1].

#5 I don't know about that. Antipsychotics don't effect opioid receptors.

 

[jasoncrest]

Thank you very much Bilz0r.

As you can see, I have edited the title into "Methadone, a SNRI?..." but it still appears as "Methadone, a NARI?...."... I don't understand...

 

[Diacetylus]

SSRIs + SSRIs cause serotonin syndrome.

I think what Bilz0r meant to say here is that SSRI's and MAOI's, or MAOI's and MDMA usage can cause serotonin syndrome.

 

[jasoncrest]

I think what Bilz0r meant to say here is that SSRI's and MAOI's, or MAOI's and MDMA usage can cause serotonin syndrome.

I remember reading somewhere that mixing 2 SSRIs can (in some rare cases I think) cause Serotonin Syndrome...

 

[BilZ0r]

No, I ment SSRIs + SSRIs. i.e. paroxetine + tramadol or paroxetine + DXM..

 

[Diacetylus]

^ahh, ok. sorry, my bad. I wasn't aware of the ssri, ssri combo leading to SS.