Posted by Cam W. on December 9, 2000, at 22:35:08
In reply to Re: Drug-Induced Weight Gain - Some Mechanisms » Cam W., posted by SLS on December 9, 2000, at 17:20:35
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> > Lisa - It probably isn't what Wellbutrin has that prevents weight gain, it is probably what it doesn't have. Wellbutrin doesn't block serotonin receptors (5-HT2C, to be exact), histaminergic (H1) receptors or muscarinic/cholinergic (M1) receptors to any appreciable extent. All of these receptors have been implicated in weight gain caused by the tricyclics (TCAs) and SSRIs.
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> Dear Cam,
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> I double-checked my SSRI weight-gain information. Isn't the fact that weight-gain occurs during increased 5-HT2C receptor stimulation resulting from SSRIs paradoxical? I thought 5-HT2C stimulation produced weight-loss and reduced appetite rather than weight-gain and hyperphagia. Fenfluramine might be a paradigm of this effect. I believe this is why the drug manufacturers noted weight-loss as predominant over weight-gain in their clinical trials and noted such in their labelling. People do lose weight on these drugs. I would love to know the true statistics in a homogeneous population of unipolar depressives. I would then like to see a comparison of weight-gain vs weight-loss in five subpopulations:
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> 1) treatment-resistant depression (TRD)
> 2) rapid poop-out
> 3) unambiguous, fully qualified atypical unipolar depression with reverse vegetative symptomology.
> 4) bipolar depression
> 5) dysthymia
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> I wonder if weight-gain is more likely to occur in these conditions. Perhaps they are indicative of a subsensitive 5-HT2C receptor polymorphism associated with depression or an idiosyncratic acceleration of 5-HT2C downregulation.
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> - ScottScott - This weight gain thing really has me baffled. You raise the same points that I have tried to resolve several times. I too, would like to see studies in this area (but who's going to fund it?). I do not really have a good grasp of what really regulates weight. With 50 to 100 neurotransmitter (or more precisely neurotransmitter-like substances - incl. nitric oxide, carbon monoxide, peptides, amino acids and several proteins, etc.) I really am finding the way the brain works to be quite facinating (so simple, yet so complex).
"If the brain were so simple that we could understand it, we would be so simple that we couldn't" - Emerson Pugh, 1997 (my addendum - "yet")
Here's another conundrum with Wellbutrin. It is a stimulating drug (esp. for the first couple of weeks, where it seems to act like a diet pill). After that, it isn't so much stimulating, but it still will keep many people awake at night, if taken too late. The wake sleep cycle is controlled (in part) in the midbrain reticular activating system. This is where the raphe nuclei are located, which contains the majority of serotonergic innervation. But Wellbutrin doesn't bind to serotonergic receptors. It is easy to say that the serotonin is affected in a round about way, but what about the converse. If you use the same logic, serotonergic antidepressants should increase stimulation of noradrenergic receptors.
It is too simplistic (reductionistic) to look at any of these neurotransmitters and receptors in isolation. The concentrations of all neurotransmitters and all receptors have to be taken into account at the same time. Since we don't know what they all are, we still can't do this. Using the analogy of building a car engine: we can fix the alternator, but the lights still don't come on.
I guess that the more I learn, the less I know. That means that I will be an expert when I convince myself that I know nothing.
In the meantime, all we can do is "Keep on Truckin'". Your pal - Cam
poster:Cam W.
thread:50044
URL: http://www.dr-bob.org/babble/20001130/msgs/50298.html