Posted by AndrewB on July 23, 2000, at 19:34:20
In reply to Look for my message-provigal failed 7/20- nm » MichaelF, posted by shellie on July 20, 2000, at 20:52:24
Michael,Thank you for sharing your experience with the Dexedrine/Stelazine combo as well as other stimulants. It is interesting to hear how different stimulants can have such widely varying effects in the same person.
By the way, are you ADD with or without the hyperactivity? What is your diagnosis?
What benefits do you notice by adding Stelazine to your Dexedrine.
What differences do notice between high and low doses of Dexedrine.
I think it is very relevant to your future medication trials to be aware that Stelazine in the low doses (1mg.) is roughly a dopamine enhancer. In low doses, as with (many) other neuroleptics, Stelazine preferential antagonizes the presynaptic dopamine autoreceptor. I assume its beneficial effects in your case are related to the antagonism of the presynaptic D2 dopamine receptor. Because of the autoreceptor’s influence on dopamine release and reuptake, its antagonism results in higher synaptic dopamine concentrations.
I always have thought that such higher concentrations of synaptic (extracellular) dopamine meant increased dopaminergic mediated nerve transmission. But upon reading the following excerpt which describes the differing effects of low and high dose stimulants, it appears that increased extracellular concentration of dopamine decreases nerve transmission:
“The anti-hyperactivity action of stimulants is mediated via post-synaptic dopamine D1 and D2 receptors. As just outlined, the enhanced output of dopamine by low doses of stimulant drugs reduces the impulse associated rise of dopamine, relative to the baseline. That is, the relative rise of dopamine during the impulse is lowered because of this elevated baseline. The smaller pulsatile surge of dopamine would result in less activation of the post-synaptic dopamine D1 and D2 receptors, thereby resulting in reduced psychomotor activity. These psychomotor-controlling dopamine receptors are hypothesized to vary their response in proportion to the relative rise in pulsatile dopamine, but there is no direct experimental work to validate this particular point. For example, the elevated extracellular dopamine would occupy more D1 and D2 receptors during rest, reducing or desensitizing these receptors from the dopamine which arrives during the nerve impulses. While this hypothesis may account for the hypolocomotor action of low doses of stimulants, high doses of stimulants cause marked elevations in the resting and pulsatile levels of extracellular dopamine, providing high enough extracellular levels of dopamine to oversaturate and overstimulate post-synaptic dopamine receptors, overwhelming the presynaptic inhibitory action of dopamine. These high levels are associated with hyperdopaminergic somatic, behavioral and psychological signs and symptoms which necessitate lowering the clinical dose.”
SOURCE: Hypothesis: “Methylphednidate elevates resting dopamine which lowers impulse-triggered release of dopamine” www.uclm.es/inabis2000/symposia/files/124/session.htmMichael, I don’t have any grand advice for you but I would like to say that you may want to try substituting Stelazine with other neuroleptics such as Zyprexa, risperidone and amisulpride. How did you respond to Wellbutrin? I’m having good results with the dopaminergic selegiline at low doses so far. It seems to substitute for a stimulant somewhat. (I’ve never taken stimulants so this is conjecture on my part. It does seem to compare closely to smooth version of amineptine.) It seems to combine well with a low dose neuroleptic for a very smooth increase in arousal and attention. In my case the neuroleptic is amisulpride. I think the neuroleptic may take away the anxiety I might feel if I were taking selegiline alone. Selegiline has been combined with a stimulant with good results. Other arousal agents to consider are Provigil, adrafinil and reboxetine.
AndrewB
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URL: http://www.dr-bob.org/babble/20000717/msgs/41270.html