refs pertaining to tolerance reversal by NMDA antagonist / Mg

[djsim]

Hi all,
Over in OD the topic re: tolerance reversal often comes up, with ppl asking whether DXM / Mg2+ / amantadine / other NMDA antagonists actually do work.

So, do they live up to "the hype"? Do you prevent tolerance or reverse it? (I'd think the former only).

If anyone has any good starting refs for me to check out I'd appreciate it. I've taken a look just now but a lot of the stuff is from 15+ yrs ago so maybe someone knows of better more recent studies?
(I have journal access BTW so I just need the refs)

thanks

sim

 

[MyExcuse]

Just to clarify, by tolerance reversal, are you speaking in general or about a particular drug related tolerance?

 

[MeDieViL]

From all the anecdotal reports i've read NMDA antagonits (particurally memantine) slows tolerane down alot but doesnt totally block it so breaks are still needed. Still very usefull in my opinion.

 

[Sturnam]

I remember reading a post by someone who said that they were taking 30 or 60mg of DXM 2x daily, and since they had started they hadn't upped their morphine dose, whereas before they would have upped the dose once or twice in the same time period. Sorry I don't have a link for this, it was a long time ago.

I guess we really have to go off of scientific articles, especially since the psychoactive/placebo effects of the NMDA antagonist would interfere with the expected outcome.

Just googled it, so I haven't read, but this looks good.


Journal Title - Psychopharmacology
Article Title - NMDA receptor antagonists inhibit opiate antinociceptive tolerance and locomotor sensitization in rats
Volume - Volume 196
Issue - 3
First Page - 497
Last Page - 509
Issue Cover Date - 2008-02-01

Author - Ian A. Mendez
Author - Keith A. Trujillo
DOI - 10.1007/s00213-007-0984-8
Link - http://www.springerlink.com/content/b44042034r413083

 

[MeDieViL]

NMDAR and ethanol tolerance:

• Ethanol-induced hypnotic tolerance is absent in N-methyl-D-aspartate receptor epsilon 1 subunit knockout mice (2006)
• Acute tolerance to ethanol inhibition of NMDA-induced responses in rat rostral ventrolateral medulla neurons (2004)
• Effect of (+)MK-801 and ketamine on rapid tolerance to ethanol (1992)
• NMDA antagonist inhibits rapid tolerance to ethanol (1991)
• Dizocilpine prevents the development of tolerance to ethanol-induced error on a circular maze test (1996)
• D-cycloserine enhances rapid tolerance to ethanol motor incoordination (1995)
• Effect of NMDA antagonists on rapid and chronic tolerance to ethanol: importance of intoxicated practice (1994)
• Interaction between N-methyl-D-aspartate (NMDA) and serotonin (5-HT) on ethanol tolerance) (1994
• Effect of D-cycloserine on rapid tolerance to ethanol (1993)
• Blockade of chronic tolerance to ethanol by the NMDA antagonist, (+)-MK-801 (1993)
• Effect of NMDA receptor antagonists on rapid tolerance to ethanol (1993)

NMDAR and benzodiazepine tolerance:

• Effect of NMDA antagonists on rapid tolerance to benzodiazepines (1997)
• The NMDA receptor competitive antagonist CPP modulates benzodiazepine tolerance and discontinuation (1997)
• Diazepam dependence prevented by glutamate antagonists (1993)

NMDAR and stimulant tolerance:

So far only found evidence of blockade to reverse tolerance, altough many anecdotal reports report a blockade of normal amphetamine tolerance.

• Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801 (1989)
• The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants (1998)
• Alteration of neuronal activities following repeated administration of stimulants (2002)

NMDAR and opioid tolerance:

• Development of morphine induced tolerance and withdrawal symptoms is attenuated by lamotrigine and magnesium sulfate in mice (2009)
• Anti-opioid action of glutamate-NMDA receptor systems underlying morphine analgesic tolerance (2009)
• Evaluation the effects of dextromethorphan and midazolam on morphine induced tolerance and dependence in mice (2008)
• The glycine site-specific NMDA antagonist (+)-HA966 enhances the effect of morphine and reverses morphine tolerance via a spinal mechanism (2008)
• NMDA receptor antagonists inhibit opiate antinociceptive tolerance and locomotor sensitization in rats (2008)

And more on pubmed about opioids, too lazy to look for everything :b

NMDAR and nicotine tolerance:

• The NMDA antagonist dizocilpine (MK-801) attenuates tolerance to nicotine in rats (1996)
• The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review (2008)
• Behavioural and neurochemical adaptations to nicotine in rats: influence of NMDA antagonists (1994)

 

[MeDieViL]

Post updated. I'd say NMDA antagonists are the key to tolerance.

 

[Symposion]

Hi.
Take a look to Jonathan's Ott research on the use of picodoses of naltrexone with opiates to boost the real opiate effects and avoid the development of tolerance.

It can be used to kill tolerance, avoid it or bloking some receptors -opiate receptors- wich functin is the opposite of the most op.receptors...
When stimulated... they make you feel pain!!
Those receptors are the ones that are silenced with those molecules of naloxone concomitant with the desired opiate.

Here in spanish:
http://rapidshare.com/files/261225828/EVITACION_SINDROME_ABSTINENCIA_-_J.OTT_-_www.DROGOTECA.com.pdf

Can't find it now in english, but it won't be difficult with these keywords: tolerance, naltrexone, codeine, Ott...

Hope it will fit in your search.

 

[The Reanimator]

@ Medievil. I guess I have nothing to say but this.