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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by jay on September 17, 2001, at 6:55:50
I am curious about any substantial differences between the effects of dopamine and and norepinephrine. I'd like to know the *pronounced* differences, as I have partial response to meds that lower/control norepinephrine levels, including many blood pressure meds. I don't know exactly how it helps, but microdoses of Clonidine is amazing for controling sweating brought on by more activating a.d.'s, anxiousness, and others have helped with sleep, to that *out of control* anxious feeling mixed anxiety/depression brings. It is not consistent, though.I am wondering about the connection between norepinephrine and cortisol secretion. Do some blood pressure meds have effects on both?
One of the last comments that I ask about this, is that in the recent *excellent* book on Depression,
'The Noonday Demon', the author states Prozac, when it was first being developed in it's infancy, was targeted as a blood pressure med by Lilly.I honestly see a lot of hope for a toning down, or regulation, of our CNS through leveling out the highly stimulating chemicals like norepinephrine, cortisol, and maybe even hormones like testosterone and estrogen.
I also wanted to add, that I don't see why they don't go for regulation of the secretion of those chemicals, rather than just receptor amounts and sensitivity. (Like they increase norepinephrine in the synapse with many a.d's to even out receptor levels. Despite the success of a.d's, it still is far from proving *major* relief for many anxious depressives.)IMHO...just curious..
Jay
Posted by Cam W. on September 17, 2001, at 7:46:12
In reply to Differences in action Dopamine and Norepinephrine?, posted by jay on September 17, 2001, at 6:55:50
Jay -
Dopamine - binds to 2 families of dopamine receptors: D1 (D1 & D5 - mainly presynaptic) and D2 (D2, D3, & D4 - mainly postsynaptic).
- affects drive, pleasure, and euphoria; also involved in cognitive integration, working memory, and the initiation of motor activity.
- stimulation of dopamine receptors can cause agitation (D3) and aggravation of psychosis (D2).
- irreversible blockade of D2 receptors ( >70%) can cause EPS and tardive dyskinesia.
- blockade of D3 receptors may play a role in the anti-anxiety/antidepressant action of Fluanxol™ (flupenthixol), an antipsychotic.•••••
Norepinephrine - binds to alpha-1, ß1 presynaptic (& somatodendritic?) and alpha-2, ß2 postsynaptic receptors.
- affects energy, interest, viligence, and self-perception; also involved in sleep maintenance and mood modulation.
- stimulation of norepinephrine receptors can cause activation, hypertension, and panic.
- alpha-1 blockade can cause drowsiness, dizziness, and hypotension.
- ß2 downregulation "may" be a step in the resolving of depressive symptoms, and "may" indirectly decrease cortisol levels by affecting CRF release from the hypothalamus &/or ACTH release from the pituitary (&/or by it's action on release of other neurotransmitters &/or neuromodulators).
- certain antihypertensives and cardiovascular drugs can precipitate or "cause" depression: digitalis, clonidine, guanethidine, methyldopa, reserpine, hydralazine, propranolol, indapamide, prazocin, procainamide, etc.•••••
As for playing with neurotransmitters, researchers will probably have better luck in "fixing" aberrant second messenger systems &/or regulating certain unique gene transcription factors or transcription products (eg. cytokines).
I hope that this is of some help. - Cam
Posted by Elizabeth on September 17, 2001, at 10:07:20
In reply to Re: Differences in action Dopamine and Norepinephrine? » jay, posted by Cam W. on September 17, 2001, at 7:46:12
Hi Cam. Could you explain what second messengers are (or more to the point, what they do)? I have a vague idea, but I'm not really clear at all. I tried asking my pdoc once and he just waved his hands around. :-)
Thanks!
-elizabeth
Posted by Cam W. on September 18, 2001, at 8:45:24
In reply to question » Cam W., posted by Elizabeth on September 17, 2001, at 10:07:20
Elizabeth - Simply stated, second messengers initiate the cascade of chemical reactions on the interior of a cell caused by a signal (produced by the binding of a molecule to a receptor on the exterior cell surface). This cascade of chemical reactions ultimately results in the transcription of genes, that will become enzymes and proteins.
The enzymes or proteins that are produced depends upon what exterior receptor is stimulated and by what molecule stimulates (or blocks) said receptor Different conformational changes in the receptor may be produced by the binding of slightly different molecules to that receptor, hence different shapes will occur on the other end of the protein (inside the cell).
Second messengers can take many forms and (I think) are driven by ATP or GTP being converted to AMP or GMP, respectively. The main second messenger is usually a G-protein. A G-protein binds to the transmembrane protein and causes a cascade of other molecules to bind to it in a very specific way (I think that the conformation of the piece of transmembrane protein sticking through to the interior of the cell dictates the type of G-protein it attracts, as well as the complement of associated molecules - I am not sure on this point, nor am I sure if the associated molecules are also referred to as secondary messengers, even though they are an integral part of the second messenger process).
An example of G-protein (second messenger) mediated intracellular reaction is the phosphoinositol pathway. Calcium ions are released from the endoplasmic reticulum, thus affecting a neuron's electrical gradient without much interference from ion channels. The exterior cellular surface receptor (protein) still spans the cell wall, but does not open into an ion channel. The conformational change of the interior portion of the protein attracts the G-protein, setting up the cascade and causing the release of calcium ions and these calcium ions further cause the release of gene products (enzymes &/or proteins). Also DAG (diacylglycerol) is released which signals PKC (protein kinase-C) which signals other G-proteins by crosstalking with other cells (PKC) is able to leave the cell and inform surrounding cells of the state of regional homoeostasis. PKC also signals the nucleus to get ready to respond with gene products.
I guess the G-protein is the quarterback of second messengers and it's complement of other molecules are the rest of the team.
Again, basically second messengers carry a signal from a receptor to the nucleus and RNA. As can be seen above (and this is only one, albeit sketchy, example of a second messenger system). There are many other second messenger systems. Since they are so specific, one could wonder about making "magic bullet" drugs to affect specific targets to" shut down" or to "fix" the signal between receptor and the transcription of gene products.
Sorry Elizabeth, this is all I can remember, without digging out my journal articles (they are still packed away in boxes, in the garage).
Take care, and I hope that this makes some sense. - Cam
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