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Memantine combined with drugs/supplements OTHER THAN psychostims


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#1 Jacovis

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Posted 09 May 2009 - 10:30 AM


Memantine and Nicotine

Not sure how FunkOdyssey's experiment turned out in the end (regarding Memantine possibly preventing/minimising tolerance to the effects of low dose Nicotine patches)...

http://www.imminst.o...amp;hl=nicotine
FunkOdyssey (February 21, 2009):
"I am developing some interest in the use of low-dose, continous delivery nicotine patches for the treatment of ADD, at a dose of 3.5 - 7mg daily. There is a saying in research circles, "nicotine is a good drug with a bad delivery system". It has shown efficacy for ADHD in several studies and performed as well as ritalin in a comparison study."

FunkOdyssey (February 21, 2009):
"...Fourteen 21mg patches are $32.99 at drugstore.com, and these can be cut into fractional pieces to produce lower doses. I was going to experiment with 1/4 of a 21mg patch, or 5.25mg, worn for about 12 hours, which should deliver about 2.625mg of nicotine in total. I assume this small of a dose would not produce significant nausea, vasoconstriction, or significant elevation of heart rate or BP. I will be monitoring for all of these potential side effects."


http://www.imminst.o...o...otine&st=30
Visionary7903 (February 21, 2009):
"...I wonder would Memantine help with tolerance issues to the effects of Nicotine patches (a lot of people get some tolerance to the effects of Nicotine patches when used regularly)?"

FunkOdyssey (February 21, 2009):
"...I'll find out, because I'm ramping up to an effective dosage of memantine right now, and it will be in place when I attempt the experiment. A little too fast actually -- I decided to be a tough guy and start at 10mg rather than 5, and I am a little makeup shy of a Left 4 Dead zombie this weekend..."


http://www.imminst.o...o...otine&st=90
FunkOdyssey (February 22, 2009):
"...I also expect [Memantine] to prevent tolerance to the motivating and focus enhancing effects of the low-dose (3.5 - 5.25mg) nicotine patches I will be experimenting with next week. I have very high hopes for these."

http://www.imminst.o...o...ermal&st=30
FunkOdyssey (March 3, 2009):
"I'm starting very cautiously with a tiny dose of 1/16th of a 21mg patch (approximately 1.3mg), in order to build some tolerance to the vasoconstriction effects before going higher. Definitely improves concentration and mental energy even at this tiny dose, however I may be extra sensitive due to pre-treatment with memantine which is an nAChR antagonist. No significant effects on blood pressure or heart rate were noted.

I remove the patch 1-2 hours before bedtime and this seems to effectively "pull the plug" on mental stimulation and facilitates quick onset of sleep. I think transdermal delivery of a stimulant with a short-half life is superior to oral tablets of long-acting stimulants, providing superior control over plasma levels and preventing insomnia."

http://www.imminst.o...o...ermal&st=60
FunkOdyssey (March 9, 2009):
"That's true, however the severity of those effects are dose-dependant. I have been experimenting with 1.3mg - 2.6mg 24 hour patches, and wearing them only 12-16 hours, for a delivered dose of .7mg - 1.7mg. I have a blood pressure and heart rate monitor and I am seeing no increase in either at these doses."


Yonsei Med J. 2008 Apr 30;49(2):175-88.
The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review.
Jain R, Mukherjee K, Balhara YP.

National Drug Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, Pin 110029, India. rakajain2001@yahoo.com

Nicotine, the primary psychoactive component of tobacco products, produces diverse neurophysiological, motivational, and behavioral effects through several brain regions and neurochemical pathways. Various neurotransmitter systems have been explored to understand the mechanisms behind nicotine tolerance, dependence, and withdrawal. Recent evidence suggests that glutamate neurotransmission has an important role in this phenomenon. The aim of the present review is to discuss preclinical findings concerning the role of N-methyl-D-aspartate (NMDA) receptor neurotransmission in mediating the behavioral effects of nicotine, tolerance, sensitization, dependence, and withdrawal. Based on preclinical findings, it is hypothesized that NMDA receptors mediate the common adaptive processes that are involved in the development, maintenance, and expression of nicotine addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists may prove to be useful in alleviating the symptoms of nicotine abstinence and facilitate tobacco-smoking cessation.

PMID: 18452252

Edited by Visionary7903, 09 May 2009 - 10:56 AM.

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#2 Jacovis

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Posted 09 May 2009 - 10:55 AM

Memantine and Caffeine

www.mindandmuscle.net/forum/
[cannot locate the source of the statement at the moment: found it through a google search and am not a member of the mindandmuscle forums]
"...I'm on Namenda right now, and it doesn't seem to be as effective for caffeine. Probably because caffeine doesn't play by the same rules as amphetamine..."

Dopaminergic agonists administered into the nucleus accumbens: Effects on extracellular glutamate and on locomotor activity

http://www.mindandmu...showtopic=35395
graatch (September 10, 2008):
Sorry, no direct studies exist. It is completely theoretical territory.

However, for our theoretical model in this use (that glutamate hyperexcitation in the nucleus accumbens core occurs secondary to amphetamine use, and that this glutamate hyperexcitation is responsible for downregulating nucleus accumbens core dopamine sensitivity, which is the additional mechanism responsible for the faster tolerance to mood/motivational effects from amphetamine than to concentrative effects, which are mostly mediated prefrontally, where there is both desensitization occurring for instance at tyrosine hydroxylase and the dopamine receptor end, and sensitization probably via neuroplastic mechanisms), there is a wide, complex, shadowy body of work to point to.

Here lesions produces by ibotenic acid (an NMDA agonist used to provoke glutamate neurotoxicity) blunt dopamine response: http://www.jneurosci...stract/16/2/714

Here chronic high cortisol (whose damaging effects seem to be largely mediated by glutamate excess) desensitizes dopamine function: http://content.karge...roduktNr=223855

With memantine (and other NMDA antagonists) decreasing the development of tolerance to opioids, the evidence is fairly extensive, you can look that up yourself. Contrary to what some may expect, opioids also seem to provoke glutamate efflux, especially chronically, and NMDA efflux is implicated in the development of nociception and tolerance to the rewarding effects of morphine.

With Boris Tabakoff's work in alcoholism, he suggests that with alcohol, too, it is glutamate-related excitotoxicity during ethanol withdrawal that desensitizes dopaminergic function in the nucleus accumbens: [url="http://www.scienceblog.com/community/older.../199900066.html...""]http://www.scienceblog.com/community/older...6.html..."[/url]


Asad Dalia1, Norman J. Uretsky and Lane J. Wallace<A href="http://www.sciencedi...b88c4dc#cor*">*

Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Accepted 9 December 1997. Available online 28 April 1998.
AbstractThe hypothesis to be tested was that increased dopaminergic transmission induced by amphetamine in the nucleus accumbens results in increased glutamatergic neurotransmission in this brain area and that the increase in level of this neurotransmitter contributes to behavioral effects of psychostimulant drugs. Amphetamine (1 mg/kg, i.p.) increased the amount of extracellular glutamate in the accumbens, as measured by in vivo dialysis, and stimulated locomotor activity. Amphetamine (10 mM) infused into the accumbens by reverse dialysis through the probe produced a similar stimulation of locomotor activity as systemic amphetamine but a greater increase in extracellular glutamate levels. Both of these responses to amphetamine were attenuated by either the selective D1 antagonist SCH23390 or the selective D2 antagonist eticlopride. The combination of a D1 and D2 agonist, SKF38393 (20 mM) and quinpirole (50 mM), administered into the accumbens by reverse dialysis also increased extracellular glutamate and stimulated locomotor activity. Administration of a glutamate uptake inhibitor, threo-β-hydroxy-aspartate (50 mM), increased extracellular glutamate but did not stimulate locomotor activity. Systemic administration of caffeine (15 mg/kg, i.p.) increased locomotor activity but did not increase extracellular levels of glutamate. These data suggest that activation of dopaminergic receptors in the nucleus accumbens results in stimulation of locomotor activity and in activation of glutamatergic transmission in this brain region. However, an increase in glutamate levels in the nucleus accumbens is neither sufficient nor necessary to produce a stimulation of locomotor activity.

http://www.mindandmu...showtopic=35395
graatch (September 11, 2008):
"...Interestingly the study [above] also found no effect of caffeine on extracellular glutamate at 15 mg/kg i.p. but this study [below] (full text) shows an effect on glutamate release in NaC at 10mg/kg i.p. : http://www.jneurosci...full/22/15/6321 . The lower dose than 10 that was tested was 3mg/kg, which showed no significant effect. The 10mg/kg dose is like ~650 mg of caffeine in humans, except before the rat conversion rate which are supposed to make it equivalent to a considerably lower dose."

http://www.jneurosci...full/22/15/6321
Caffeine Induces Dopamine and Glutamate Release in the Shell of the Nucleus Accumbens

Marcello Solinas, Sergi Ferré, Zhi-Bing You, Marzena Karcz-Kubicha, Patrizia Popoli, and Steven R. Goldberg
Sections of 1 Preclinical Pharmacology and 2 Behavioral Neuroscience, Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health Intramural Research Program, Baltimore, Maryland 21224, and 3 Department of Pharmacology, Istituto Superiore di Sanita, 00161 Rome, Italy

Abstract
An increase in the extracellular concentration of dopamine in the nucleus accumbens (NAc) is believed to be one of the main mechanisms involved in the rewarding and motor-activating properties of psychostimulants such as amphetamines and cocaine. Using in vivo microdialysis in freely moving rats, we demonstrate that systemic administration of behaviorally relevant doses of caffeine can preferentially increase extracellular levels of dopamine and glutamate in the shell of the NAc. These effects could be reproduced by the administration of a selective adenosine A1 receptor antagonist but not by a selective adenosine A2A receptor antagonist. This suggests that caffeine, because of its ability to block adenosine A1 receptors, shares neurochemical properties with other psychostimulants, which could contribute to the widespread consumption of caffeine-containing beverages.

Discussion
Dopamine release in either the core or the shell of the NAc has been suggested to be causally related to the locomotor stimulant effects of psychostimulants such as amphetamine (Parkinson et al., 1999; Boye et al., 2001), whereas preferential release of dopamine in the shell of the accumbens has been suggested to be causally related to the rewarding effects of psychostimulants (Di Chiara and Imperato, 1988). The close correlations between the motor-activating effects and the previously described discriminative-stimulus effects of caffeine (Mumford and Holtzman, 1991) and the present microdialysis data are consistent with the possibility that the preferential release of dopamine and glutamate in the shell of the NAc may also be involved in the psychostimulant effects of caffeine. Our hypothesis might seem to be in conflict with the studies by Joyce and Koob (1981), who found that 6-hydroxydopamine lesions in the region of the NAc of rats blocked the locomotor activation induced by amphetamines but failed to block the locomotor activation induced by caffeine. Based on these results, the authors suggested that caffeine induces locomotor activity by acting independently of presynaptic terminals in the mesolimbic dopaminergic system (Joyce and Koob, 1981; Swerdlow et al., 1986). However, in view of the demonstrated resistance to 6-hydroxydopamine-induced dopamine denervation in the shell versus the core of the NAc (Meredith et al., 1995; Boye et al., 2001), those studies cannot rule out a preferential role of dopamine release in the shell of the NAc on the motor effects induced by caffeine. Nevertheless, it must be pointed out that other striatal regions can also be involved, because a significant although less pronounced effect of caffeine on dopamine release was also observed in the core of the NAc (see the introductory remarks; Morgan and Vestal, 1989). Surprisingly, the highest dose of caffeine (100 mg/kg) did not produce any effect on extracellular dopamine or glutamate levels in the shell of the NAc. Additional studies are needed to clarify the mechanisms involved in this lack of effect. However, high doses of caffeine are known to exert effects through mechanisms other than adenosine receptor antagonism (e.g., phosphodiesterase inhibition and release of intracellular calcium) (Daly and Fredholm, 1998).

The results obtained with the selective adenosine A1 and A2A receptor antagonists indicate that the effects of the lower 10 and 30 mg/kg doses of caffeine on dopamine and glutamate release are related to adenosine A1 receptor antagonism. Thus, although blockade of adenosine A2A receptors is currently believed to be the main mechanism responsible for the behavioral-activating (psychostimulant) effects of caffeine (Daly and Fredholm, 1998), as suggested previously (Snyder et al., 1981; Nikodijevic et al., 1991; Kaplan et al., 1992; Popoli et al., 1998), blockade of adenosine A1 receptors also may play a relevant role. At the dose used in the present study, the A2A receptor antagonist had been shown previously to induce pronounced motor activation (Popoli et al., 1998). This rules out the possibility that the motor response is responsible for the dopamine release in the NAc induced by caffeine or the A1 receptor antagonist. The most probable localization of the adenosine A1 receptors that modulate caffeine-induced elevations in extracellular dopamine and glutamate levels is in the terminals of dopaminergic and glutamatergic afferents to the NAc. In fact, there is morphological and functional evidence for this presynaptic localization of adenosine A1 receptors (Wood et al., 1989; Okada et al., 1996; Flagmeyer et al., 1997; Golembiowska and Zylewska, 1997). Also, microdialysis studies have shown previously that the striatal perfusion of A1 receptor agonists and antagonists significantly modifies (decreases and increases, respectively) the striatal extracellular concentrations of dopamine and glutamate (Okada et al., 1996; Golembiowska and Zylewska, 1997). Finally, the increase in the extracellular levels of dopamine induced by caffeine and the A1 receptor antagonist could be related to their effects on extracellular glutamate, in view of the evidence for a facilitatory role of glutamate on striatal dopamine release (Morari et al., 1998).

The region-dependent effects of caffeine in the NAc are similar to those produced by other psychostimulants and addictive drugs, such as amphetamine, cocaine, morphine, heroin, nicotine or 9-tetrahydrocannabinol (9-THC), all of which preferentially increase extracellular levels of dopamine in the shell of the NAc (Pontieri et al., 1995). Although the degree of increase in extracellular dopamine levels induced by caffeine is lower than that induced by amphetamine and cocaine, it is in the same range as increases induced by the systemic administration of nicotine (Di Chiara and Imperato, 1988), 9-THC (Chen et al., 1991), morphine (Di Chiara and Imperato, 1988; Pontieri et al., 1995), or ethanol (Di Chiara and Imperato, 1988). Because these neurochemical changes are often considered central to the development of drug dependence, they could contribute to the widespread consumption of caffeine-containing beverages.

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#3 bgwithadd

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Posted 09 May 2009 - 08:55 PM

Nicotine doesn't really get tolerance. Nicotine plus memantine is a little much, though, and makes me feel kind of crazed.

Caffeine gets tolerance but not in the same way. It has negative effects that can't really be countered except by things that decrease cAMP.

#4 doctordog

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Posted 11 May 2009 - 01:50 AM

how about memantine combined with an NDMA agonist like glycine?

#5 FunkOdyssey

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Posted 11 May 2009 - 06:07 AM

I actually could never really get going with my nicotine experimentation because it was causing me chest pain every time. That will have to wait until I've made more progress with the Lyme treatment.

#6 blazewind

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Posted 11 May 2009 - 07:48 AM

Wow, I can't believe I have not realized this before. This will take time to formulate into coherent words, but for now: there is a "window" of things that will be saved to long term memory. There is a concept in neuroscience called "downscaling" that sleep is erasing "irrelevant" memories by erasing synapses that do not pass a certain threshold. I believe that NMDA antagonists may be able to create a ceiling so more information can fit into the window of things saved to long term memory. To get more information into that window of long term memory, we need to both increase the function of receptors while also limiting the ceiling that a circuit could fire so the synaptic potentiation could be more even... the analogy that really put this together for me is the concept of dynamic range in music, and how music is becoming more compressed into the top range. If you are interested in understanding my theory, try reading this article "The Death Of Dynamic Range" http://www.cdmasteri...ynamicdeath.htm and change the loudness to synaptic strength and realize that the bottom half of things below a certain threshold are being cut off to "erase the synapses" so to enhance memory, we need to actually decrease the "dynamic range" I have insufficient evidence to back this up, just a wild idea at the moment.
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#7 doctordog

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Posted 12 May 2009 - 07:49 AM

please forgive the bombardment of questions, but i have one more concern which was sparked by a meeting with my GP today, in which i informed him that i was trialing Memantine. he said that i did not seem to present the characteristics of glutamate overactivity (which would conventionally call for him to prescribe Neurontin); if anything, given my persistent anhedonia, faltering memory, etc. he thought it might be a case of the opposite. i realise memantine's status as a partial antagonist means that it only activitates in the face of potential exitotocity, but does that also mean itgoes some way towards restoring homoeostasis in an underactive glumate system? or would it be best combined with an extraneous stimulant?

#8 bgwithadd

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Posted 12 May 2009 - 11:05 AM

It's unlikely you have underactive glutamate system. If you did you would feel like your head was made of lead but no real symptoms like that. That's probably low dopamine transport or low dopamine or low NE.

#9 doctordog

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Posted 12 May 2009 - 12:45 PM

It's unlikely you have underactive glutamate system. If you did you would feel like your head was made of lead but no real symptoms like that. That's probably low dopamine transport or low dopamine or low NE.


well that makes sense. i admit i was suspicious about his claim, and proposed that DA might be playing some role instead, to which he replied he would sooner introduce DLPA over Ritalin or Adderall, but only once i had a firmer grasp on what memantine itself was doing.

#10 Jacovis

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Posted 14 May 2009 - 10:06 AM

Memantine and Low Dose Naltrexone (LDN)

doi:10.1016/j.ejphar.2008.02.015


Copyright © 2008 Elsevier B.V. All rights reserved.
Short communication

Memantine enhances the inhibitory effects of naltrexone on ethanol consumption


Alexander Kuzmin, a, , Tove Stenbacka and Sture Liljequista

aDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden


Received 21 June 2007; revised 17 January 2008; accepted 6 February 2008. Available online 14 February 2008.
Abstract

Effects of the opioid receptor antagonist naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) on operant ethanol self-administration alone and in combination with the non-competitive NMDA antagonist memantine (0.5 and 1 mg/kg, i.p.) were studied in rats. Acute administration of naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) inhibited ethanol self-administration in a dose-dependent manner. Memantine (1.0 mg/kg) significantly enhanced the effects of naltrexone at 0.1 mg/kg, failing per se to inhibit ethanol consumption. Thus, low, sub-effective dose of memantine in combination with low doses of naltrexone blocked the reinforcing properties of ethanol in rats. It is suggested that the combination of sub-effective doses of memantine and naltrexone may have therapeutic value in the treatment of alcoholism particularly in a subgroup of alcoholic patients who have high sensitivity to the adverse side effects of naltrexone.

Keywords: Ethanol; Reward; Naltrexone; Memantine; Self-administration

#11 Jacovis

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Posted 14 May 2009 - 11:20 AM

Nicotine doesn't really get tolerance. Nicotine plus memantine is a little much, though, and makes me feel kind of crazed.

Caffeine gets tolerance but not in the same way. It has negative effects that can't really be countered except by things that decrease cAMP.


I actually could never really get going with my nicotine experimentation because it was causing me chest pain every time. That will have to wait until I've made more progress with the Lyme treatment.


Okay thanks for everyone's thoughts/updates.
What do you guys think about Memantine as a counter to the tolerance that rapidly develops to Tyrosine supplementation (has anyone tried this)?

What do you think of combining highly bioavailable forms of all the dopamine/noradrenaline precursors with Memantine:
say
N-Acetyl-Tyrosine
Sublingual Pyridoxal-L-Phosphate (that's activated Vitamin B6)
Sublingual NAD (that's activated Vitamin B3)
Methylcobalamin (that's activated Vitamin B12)
Folinic Acid or L-Methylfolate (that's activated Folic Acid)
Calcium Ascorbate (for Vitamin C)
Copper
Iron
Zinc
Magnesium
Manganese
possibly all the other B Vitamins as well to ensure balance

all together with Memantine?

I know there is no evidence, but from my reading and experience:
- Memantine + Dextroamphetamine felt quite different to the first few days of Dextroamphetamine alone.
I believe it isn't just a case of Memantine 'reducing tolerance' to Dextroamphetamine's effects so I am curious what Memantine could do with other things that raise Dopamine (I know that's definitely not the only thing that Amphetamines do) and Noradrenaline even...

#12 bgwithadd

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Posted 14 May 2009 - 11:29 AM

The tyrosine route is possible, but verall, it makes anything dopaminergic harder and will just cause more honeostasis clampdown due to its effects there. I think that deprenyl + memantine + DLPA seems to work, though, without pulling me into a weird out of body shadow realm like when I had PEA in the mix.

#13 FunkOdyssey

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Posted 14 May 2009 - 02:01 PM

I don't think memantine and tyrosine would work, since IIRC downregulation of tyrosine hydroxylase is the primary homeostatic response to tyrosine supplementation and memantine would not have any effect there.

#14 edward

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Posted 14 May 2009 - 03:25 PM

Memantine, which I have taken continuously for about 6 months or so is some great stuff by itself (once you get over the ramp up period) however it doesn't do much for nicotine tolerance. What I have found that works great for nicotine tolerance is to take two days off of nicotine per week and instead take 4 mg of galantamine bid on the off days as a nicotine substitute. Galantamine is a modulator at the nicotinic ACH receptors and seems to have the effect of reseting them and making them more sensitive.

edit: Not my idea, a biochemist I know stumbled on this and passed on the information.

Edited by edward, 14 May 2009 - 03:26 PM.

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#15 tjcbs

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Posted 21 October 2010 - 10:03 PM

Does anyone have any info or experience w/ combining memantine and MJ?

#16 medievil

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Posted 21 October 2010 - 10:07 PM

I don't think memantine and tyrosine would work, since IIRC downregulation of tyrosine hydroxylase is the primary homeostatic response to tyrosine supplementation and memantine would not have any effect there.

Dizocilpine enhances striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase activity

Maria Hadjiconstantinoua, b, c, , *, Zvani L. Rossettib, Trina A. Wemlingerb and Norton H. Neffc, b
a Department of Psychiatry, The Ohio State University College of Medicine, 333 W. 10th Avenue, Columbus, OH 43210, USA
b Department of Pharmacology, The Ohio State University College of Medicine, Columbus, OH 43210, USA
c Neuroscience Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA
Received 31 August 1994; revised 28 November 1994; accepted 6 December 1994. ; Available online 24 January 2003.
Abstract
Dizocilpine administration enhances dopamine metabolism in the rat striatum, nucleus accumbens, olfactory tubercle, and prefrontal cortex. Concomitant with increased metabolism is enhanced tyrosine hydroxylase and aromatic L-amino acid decarboxylase activities in the striatum and increased mRNA for the two enzymes in the midbrain. Activation of dopaminergic neurons may, in part, explain increased locomotor activity in normal animals and the ability of dizocilpine to potentiate the antiparkinsonian action of -3,4-dihydroxyphenylalanine in an animal model.

Effects of glutamate antagonists on the activity of aromatic L-amino acid decarboxylase

Abstract
This study examines the hypothesis that glutamate tonically suppresses the activity of the enzyme aromatic L-amino acid decarboxylase (AADC), and hence the biosynthesis of dopamine, to explain how antagonists of glutamate receptors might potentiale the motor actions of L-DOPA in animal models of Parkinson's disease. A variety of glutamate antagonists were therefore administered acutely to normal rats, which were sacrificed 30–60 min later and AADC activity assayed in the substantia nigra pars reticulate (SNr) and corpus striatum (CS). The NMDA receptor-ion channel antagonists MK 801, budipine, amantadine, memantine and dextromethorphan all caused a pronounced in creased in AADC activity, more especially in the SNr than CS. The NMDA glycine site antagonist ®-HA 966 produced a modest increase in AADC activity in the CS but not SNr, whilst the NMDA polyamine site antagonist eliprodil, the NMDA competitive antagonist CGP 40116 and the AMPA antagonist NBQX were without effect. The results suggest that an increase in dopamine synthesis might contribute to the L-DOPA-facilitating actions of some glutamate antagonists.


NMDA antagonists facilate aromatic L-amino acid decarboxylase and tyrosine hydroxylase.

#17 medievil

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Posted 21 October 2010 - 10:08 PM

Memantine, which I have taken continuously for about 6 months or so is some great stuff by itself (once you get over the ramp up period) however it doesn't do much for nicotine tolerance. What I have found that works great for nicotine tolerance is to take two days off of nicotine per week and instead take 4 mg of galantamine bid on the off days as a nicotine substitute. Galantamine is a modulator at the nicotinic ACH receptors and seems to have the effect of reseting them and making them more sensitive.

edit: Not my idea, a biochemist I know stumbled on this and passed on the information.

I found that it did work for nicotine tolerance at 40mg /day. YMMV.

Edited by medievil, 21 October 2010 - 10:11 PM.


#18 fern

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Posted 04 December 2010 - 10:56 PM

Memantine and Low Dose Naltrexone (LDN)

doi:10.1016/j.ejphar.2008.02.015


Copyright © 2008 Elsevier B.V. All rights reserved.
Short communication

Memantine enhances the inhibitory effects of naltrexone on ethanol consumption


Alexander Kuzmin, a, , Tove Stenbacka and Sture Liljequista

aDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden


Received 21 June 2007; revised 17 January 2008; accepted 6 February 2008. Available online 14 February 2008.
Abstract

Effects of the opioid receptor antagonist naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) on operant ethanol self-administration alone and in combination with the non-competitive NMDA antagonist memantine (0.5 and 1 mg/kg, i.p.) were studied in rats. Acute administration of naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) inhibited ethanol self-administration in a dose-dependent manner. Memantine (1.0 mg/kg) significantly enhanced the effects of naltrexone at 0.1 mg/kg, failing per se to inhibit ethanol consumption. Thus, low, sub-effective dose of memantine in combination with low doses of naltrexone blocked the reinforcing properties of ethanol in rats. It is suggested that the combination of sub-effective doses of memantine and naltrexone may have therapeutic value in the treatment of alcoholism particularly in a subgroup of alcoholic patients who have high sensitivity to the adverse side effects of naltrexone.

Keywords: Ethanol; Reward; Naltrexone; Memantine; Self-administration

Does this study imply that memantine and LDN are incompatible with each other? Seems that way, prob something people on this forum who might dabble in both should be aware of. Also wonder if the full paper has some sort of algorithm for memantine's modulation of naltrexone... perhaps it would still be viable at sub-mg doses, or something along those lines. It would be a real shame if trying memantine would mean having to go off ldn.

#19 chrono

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Posted 05 December 2010 - 07:31 PM

Does this study imply that memantine and LDN are incompatible with each other? Seems that way, prob something people on this forum who might dabble in both should be aware of.

I don't think the abstract suggests that. Quite the opposite: "Memantine (1.0 mg/kg) significantly enhanced the effects of naltrexone at 0.1 mg/kg." Note that this study was only concerned with the overlapping anti-craving properties of these drugs, so this doesn't mean that other mechanisms and effects will necessarily interact. Also, the abstract only mentions an effect at 1.0mg/kg memantine and 0.1mg/kg naltrexone, which implies that potentiation did not occur at the other five dosage combinations.

These dosages correspond very roughly to 1mg LDN and 10mg memantine for humans, so there's some possibility of clinically relevant interaction. But without more data, it seems premature to assume that it would actually matter. If anything, caution may be warranted if enhanced effects of either drug would be undesirable—though ironically, increasing the dose of naltrexone might actually eliminate its potentiation by memantine.

Edited by chrono, 05 December 2010 - 07:34 PM.


#20 satsumass

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Posted 29 June 2012 - 08:06 PM

I know this is an old thread, but I'm really curious if anyoen else has tried LDN and HIGH dose memantine....i've been using 50mg memantine over the past few weeks for bipolar 2 depression, some obsessional tendencies, fairly effedtively. I have also used LDN in the past and periodically through the past few weeks as well. I thought the LDN was actually pretty effecdtive for my depression last year when I used it for a period of time, but I also think it messed with sleep pretty badly although i think sleep apnea was unreleated to LDN unless there is something I don't know....anyway, just interested...anything else I should know about the benefits/risks of LDN with memantine?

Does this study imply that memantine and LDN are incompatible with each other? Seems that way, prob something people on this forum who might dabble in both should be aware of.

I don't think the abstract suggests that. Quite the opposite: "Memantine (1.0 mg/kg) significantly enhanced the effects of naltrexone at 0.1 mg/kg." Note that this study was only concerned with the overlapping anti-craving properties of these drugs, so this doesn't mean that other mechanisms and effects will necessarily interact. Also, the abstract only mentions an effect at 1.0mg/kg memantine and 0.1mg/kg naltrexone, which implies that potentiation did not occur at the other five dosage combinations.

These dosages correspond very roughly to 1mg LDN and 10mg memantine for humans, so there's some possibility of clinically relevant interaction. But without more data, it seems premature to assume that it would actually matter. If anything, caution may be warranted if enhanced effects of either drug would be undesirable—though ironically, increasing the dose of naltrexone might actually eliminate its potentiation by memantine.



#21 riloal

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Posted 17 August 2012 - 09:39 AM

Bump, i,m also interested in the combo LDN with memantine,. Anyone it,s on the combo? Thanks

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#22 satsumass

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Posted 17 August 2012 - 09:56 PM

BUMP BUMP BUMP...anyone? I'm trippin' right now on a bit of an OD of memantine. I was averaging 40mg a day and I stupidly popped an exstra 3 10mg pills today....and wow....total dissassociative high....really out of it. Would the LDN i'm on (4.0mg) have an impact too? Did we ever figure out how memantine and LDN would interact on a pragmatic level?




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