Posted by btnd on September 28, 2003, at 9:18:54
In reply to Here are NMDA antagonist dosages / MorphiDex » btnd, posted by Ame Sans Vie on September 28, 2003, at 8:28:51
Thanks Ame for the info!
> I'm not finding anything specifically addressing the issue of NMDA-antagonists for amphetamine tolerance, but I did come across a lot concerning their use to potentiate and prevent tolerance to opioids as well as the potential for them to have such an impact upon dependence/tolerance in general.
I hope andrewb won't mind if I cut/paste some of his great information on amphetamine tolerance and NDMA antagonism:"For some individuals, amotivation and anergia are only partially resolved by taking selegiline. For these individuals, an amphetamine or related stimulants will, for most, resolve any remaining anergia and amotivation. However, for most, tolerance for these stimulants? motivational and energizing effects develops. Therefore, an agent to prevent tolerance, e.g. an NMDA (partial) antagonist, may also be required, as discussed further on. When the appropriate stimulant at the appropriate dosage, with the proper NMDA antagonist are taken, an individual may achieve normal to robust energy and drive (proper enthusiasm for life) on an ongoing basis"
...
"It is normal for tolerance to develop over time for many or all of amphetamines effects. Tolerance may occurs slowly over a period of months, with all the positive effects fading away over times except those associated with features of apathy. Alternatively, tolerance may develop quickly, within a period of, say, 3 to 6 days. When the ?crash? comes, the individual is left irritable and dysphoric. However, if the amphetamines are stopped for 1 or 2 days, the full effect of the amphetamine is restored. In ADD, these breaks from taking amphetamine to restore effect are termed ?drug holidays?.
Amphetamine tolerance is caused by excess Ca++ influx through the NMDA receptor gated calcium channels on the outer membranes of the dopamine cells bodies in the ventral tegental area, one of two areas in the brain with concentrations of dopamine producing neurons.
As alluded to above, taking an appropriate NMDA antagonist will prevent the development of a tolerance for the effects of an amphetamine or amphetamine-like stimulant. Also by preventing excess Ca++ influx into the neuron, an NMDA antagonist will prevent associated brain alterations and damage (excitotoxicity).
Many studies have indicated that amphetamine tolerance is prevented by exogenous or endogenous agents that are able to inhibit excess Ca+ influx into the neuron through the gated calcium channels on the neuronal membrane that have NMDA subtype glutamate receptors. Glutamate, the body?s major excitatory neurotransmitter, opens the gated calcium ion channels upon attaching to the NMDA receptor. A number of other receptors are also expressed on these calcium channels, which, when stimulated, either facilitate or inhibit glutamate?s action.
Excess Ca++ influx has been implicated in a number of neurodegenerative disorders and depressive processes. That being said, calcium channel activity is essential for brain function. Without it, neurotransmission would not occur. Furthermore, deficient calcium channel activity is also associated with neurodegeneration and the development of certain neurological pathologies.
Therefore it is important that agents that inhibit calcium channel activity not also cause deficient Ca++ influx. For example, ketamine is a NMDA receptor full antagonist that prevents excess Ca++ influx and amphetamine tolerance. But, being a full NMDA antagonist, ketamine in excessive doses results in deficient Ca++ influx. Besides being damaging to the brain, it causes severe memory loss and states of disassociation. Perhaps you?ve heard of ketamine by its street names; PCP, angel dust.
Two agents with minimal or no side effects have been identified as preventing amphetamine tolerance, memantine and acamprosate."
poster:btnd
thread:263518
URL: http://www.dr-bob.org/babble/20030928/msgs/263891.html