Posted by PeterJ on April 27, 2000, at 0:33:49
In reply to More Qs for PeterJ, posted by AndrewB on April 26, 2000, at 11:07:18
> 1) Are there rough equivalents to amineptine. For example, are COMT inhibitors possibly substitutes since they would result in >increased dopamine in the synaptic clefts as does amineptine. By the way, does it seem like COMT inhibitors have AD potential >either alone or in combo with an MAO-A, MAO-I or L-Dopa.
COMT inibitors may have some anidepressant potential. See the other thread on this topic.
The closest equivalents to amineptine might be stimulants such as dexedrin, ritalin, mazindol or diethylpropion. Other drugs known to effectively enhance dopamine are MAOIs (deprenyl in particular), l-dopa, direct agonists such as bromocriptine or pramipexole, presynaptic antagonists such as sulpiride and possibly other drugs such as bupropion.> 2) Can tyrosine supplementation potentiate the effect of amineptine. One person stated that tyrosine potentiated dexadrine by >preventing dopamine depletion. Amphetamines like dexadrine are D2 reuptake blockers. Amineptine has similar mechanics, being >a dopamine reuptake blocker.
I would expect tyrosine to have some potentiating effect. In animal studies, tyrosine conversion to dopamine is increased in situations of increased dopamine turnover. In human studies, delpletion of serum tyrosine has been shown to prevent the stimulant effects of amphetamine. Thus tyrosine might reduce any dopamine depletion by amineptine. The magnitude of this effect and whether or not it would prevent withdrawal symptoms is harder to estimate. Tyrosine does seem to have modest clinical benefits in some cases of depression or stimulant addiction.
> 3) Is it important to use a dopamine neuron neuroprotective agent such as pramipexole (a D2 agonist) when using agents such as >amineptine that raise dopamine levels. Pramipexole may provide its neuroprotective effects through the depression of dopamine >metabolism, antioxidant effects and the stimulation of trophic activity.
Amineptine and similar drugs are not likely to damage dopamine neurons unless taken in extremely high doses. Thus I would not be too worried about neuroprotection in the short term. There might be some logic in taking pramipexole in the long term. It may also have antidepressant properties itself.
In terms of enhancing dopamine activity and protecting dopamine neurons, the MAOI deprenyl (selegeline, eldepryl) should be mentioned. It is a standard Parkinsons treamtment due to its dopamine boosing effect. It also prevents the activation of certain toxins which may damage dopamine neurons.> 4) Is it possible for exercise to deplete dopamine and NE stores. After hard exercise, when unmedicated, I experience extreme >mental fatigue following exercise. It starts maybe 12 hours (the next morning) after the exercise and lasts for maybe three days >after that. Symptoms include loss of memory, mental confusion, busy head (increased internal dialogue, often self critical), lack of >vigilance, physical fatigue, irritability, dysphoria, feelings of vulnerability, feelings of indecision, tiredness, spots and worms >(floaters) in visual field sometimes accompanied by vertigo and mild orthostatic hypotension. It can get so bad that I’m not able to >remember my own phone number or do simple number tasks. NE and dopamine (especially D2,D3) receptor transmission >enhancers such as amisulpride and reboxetine are able to completely take away these symptoms except for the muscle soreness.
> The muscle soreness is taken away by high doses of 7-keto DHEA.Exercise may well deplete dopamine and norepinephrine. There is some laboratory evidence of this. Clincally, Dr. Birkmayer of Vienna, a leading Parkinsons expert, has observed a worsening of symptoms immediately following exercise, which he attributes to dopamine depletion.
Perturbations of the hypothalamic-pituitary-adrenal axis may also be a factor in exercise fatigue. Interestingly, serotonin may increase fatigue after exercise.
I am encouraged to hear you have gotten good results for this symptom from amisulpiride and reboxetine. I have similar symptoms myself. How would you compare the effects of amisulpiride vs. reboxetine?> 5) Does D1 receptor stimulation potentiate D2 receptor function. Does serotonin potentiate D2 receptor function. There is >apparently a complex interrelationship of potentiation and inhibition between different dopamine receptors. Also, it is thought that >part of the AD effect of serotenergic ADs is due to enhancement of D2 function.
I have an entire book in my collection called "D1 D2 Receptor Interactions." I can't summarize it all right now, but generally D1 stimulation does potentiate D2. In fact, in some cases a minimum of D1 stimulation is necessary before D2 stimulation has any effect. This does not apply to presynaptic D2 receptors which are independant of D1. I'm still trying to figure out the clinical implications of this. D1/D2 interactions may affect circadian rhythms.
> Sorry to ask so many questions. They all however are so important to me.
> Sincerely,
>AndrewBAs I am in a similar situation myself, I understand the desire to ask questions.
Peter
poster:PeterJ
thread:30864
URL: http://www.dr-bob.org/babble/20000420/msgs/31421.html