![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 23 to 47 of 56. Go back in thread:
Posted by Cam W. on April 11, 2000, at 23:19:39
In reply to Re: sign me up! (to liz)/CarolAnn, posted by liz on April 11, 2000, at 20:25:44
liz - Sorry, I don't know the drug; and sexual function involves so many different receptors. Scientists are still fighting over what causes SSRI-induced delayed orgasms. I can't seem to get a straight answer anywhere, the deeper I look into the subject.A hypothesis - An increase in circulating dopamine may decrease serotonin levels, as the two interact opposingly. Decreased serotonin would lead to decreased serotonin-2A receptor stimulation (if indeed that is what is causing SSRI-induced sexual problems), thus resolving the delayed orgasm. The downside is what is the decrease in serotonin doing to the depression? Maybe nothing, as when we deplete someone of serotonin, they do not get depression. Decreased levels of serotonin are just a symptom of depression and these symptoms can be resolved by increasing serotonin. I don't know.
Thinking out loud - Cam W.
Posted by AndrewB on April 12, 2000, at 9:45:11
In reply to Re: clarification, please read everyone(esp. Cam), posted by liz on April 11, 2000, at 8:30:48
Uprima is more commonly known as apomorphine. I guess that Uprima is the trade name that they will market apomorphine under as a medicine for sexual dysfunction. Apomorphine has been around quite awhile and is used as a drug to help with parkinsons disease. It is both a D2 and D1 receptor agonist. Like many other dopamine agonists (bromocriptine, pergolide, lisuride) and dopaminergenics (selegiline), it has been noted to have the ability to enhance sexual function in both men and women. Apomorphine has been used off label for quite some time as a sexual enhancer. Its relatively short half-life (1-2 hours) makes it well suited for this purpose. I believe Uprima will be in a sublingual form. Side effects include nausea, which is common with dopamine agonists. Domperidone, a peripheal dopamine receptor blocker, offsets the nausea but is available only in Europe.
From all that I have read, excepting this CNN story you refer to Liz, apomorphine is a libido enhancer. It works in both men and women. Its action is most probably through the stimulation of the central D2 receptors. Its ultimate action may be due to the release the hormone oxytocin or the lowering of the level of the hormone prolactin. I wonder if the CNN story isn't correct also and possibly these hormones have an effect on vasodialation in the genital area of both men and women.
AndrewB
Posted by liz on April 12, 2000, at 9:50:06
In reply to Re:to liz - serotonin and dopamine - musings, posted by Cam W. on April 11, 2000, at 23:19:39
Cam, when you muse like this my eyes start to cross. I certainly don't have your science background and couldn't get it if I tried. I sort of preferred the little drawing on the TV screen, where they drew on a schematic a red line that went straight from the hypothalamus to the crotch. Now that I could understand! Sometimes ya gotta just take this stuff as an act of faith, lay back and enjoy the results! (I hope you can tell that my inflection is entirely teasing :-O ) Liz
liz - Sorry, I don't know the drug; and sexual function involves so many different receptors. Scientists are still fighting over what causes SSRI-induced delayed orgasms. I can't seem to get a straight answer anywhere, the deeper I look into the subject.
>
> A hypothesis - An increase in circulating dopamine may decrease serotonin levels, as the two interact opposingly. Decreased serotonin would lead to decreased serotonin-2A receptor stimulation (if indeed that is what is causing SSRI-induced sexual problems), thus resolving the delayed orgasm. The downside is what is the decrease in serotonin doing to the depression? Maybe nothing, as when we deplete someone of serotonin, they do not get depression. Decreased levels of serotonin are just a symptom of depression and these symptoms can be resolved by increasing serotonin. I don't know.
>
> Thinking out loud - Cam W.
Posted by liz on April 12, 2000, at 10:28:11
In reply to Re: Uprima, apomorphine, posted by AndrewB on April 12, 2000, at 9:45:11
Andrew, thanks for the interesting input! My Dad has Parkinson's disease; I don't believe he has ever been on Apomorphine, but perhaps he should be!
Anyway, you are correct that Uprima is to be taken sublingually. CNN also touched briefly on the approval hearings; apparently the (rare) side effects of the drug during trials were fainting or passing out, even some sudden heart failures, although the controversy has been if those effects could be unequivicably attributed to the drug. Understandably, those results and the surrounding controversy have slowed down the approval process.
BTW, what does "off label" mean?
************************************************
Uprima is more commonly known as apomorphine. I guess that Uprima is the trade name that they will market apomorphine under as a medicine for sexual dysfunction. Apomorphine has been around quite awhile and is used as a drug to help with parkinsons disease. It is both a D2 and D1 receptor agonist. Like many other dopamine agonists (bromocriptine, pergolide, lisuride) and dopaminergenics (selegiline), it has been noted to have the ability to enhance sexual function in both men and women. Apomorphine has been used off label for quite some time as a sexual enhancer. Its relatively short half-life (1-2 hours) makes it well suited for this purpose. I believe Uprima will be in a sublingual form. Side effects include nausea, which is common with dopamine agonists. Domperidone, a peripheal dopamine receptor blocker, offsets the nausea but is available only in Europe.
>
> From all that I have read, excepting this CNN story you refer to Liz, apomorphine is a libido enhancer. It works in both men and women. Its action is most probably through the stimulation of the central D2 receptors. Its ultimate action may be due to the release the hormone oxytocin or the lowering of the level of the hormone prolactin. I wonder if the CNN story isn't correct also and possibly these hormones have an effect on vasodialation in the genital area of both men and women.
>
> AndrewB
Posted by Fred Potter on April 12, 2000, at 20:48:29
In reply to Re: Uprima, apomorphine, posted by AndrewB on April 12, 2000, at 9:45:11
How can you have sex when you feel sick?
Posted by liz on April 12, 2000, at 21:12:47
In reply to Re: Uprima, posted by Fred Potter on April 12, 2000, at 20:48:29
Fred, hello. Well, some of us don't have much choice, our spouses or partners feel fine! Also, for some of us, the "timeout" from illness through sex can be pretty healing. I feel like I need to apologize, but I've pretty much enjoyed sex with my husband, even when I haven't been in the mood or am not well. There is something, ideally, about closeness that is very healing and comforting, INHO. I don't think anyone should feel compelled to have a sexual relationship; it is certainly not the cure for everything that ails us, but it has its merits. Ummm, maybe its different for women; we have the luxury of being somewhat passive and I know men do not, as a rule.
How can you have sex when you feel sick?
Posted by Scott L. Schofield on April 13, 2000, at 7:51:08
In reply to Re: Uprima/Fred, posted by liz on April 12, 2000, at 21:12:47
>> How can you have sex when you feel sick?
> I feel like I need to apologize, but I've pretty much enjoyed sex with my husband, even when I haven't been in the mood or am not well. There is something, ideally, about closeness that is very healing and comforting, INHO.
I agree with this. This has been my experience as well.
I really don't mean this to be one of my stupid play on words, but for me, sex is in the head.
Bipolar depression has left my libido as being close to nil. However, my desire remains high. I know this at first seems to be contradictory, but I do not equate the word "desire" with "libido". I just like to have sex. I like to eat too, even when I'm not hungry.
My last heavy-duty sexual relationship was with a girl who suffered from depression as well. Actually, she suffered from double-depression. She knew exactly what it felt like to not have a libido. With the exception of a two-month period of severe depression, she remained in a state of dysthymia while we were together. During the previous eight years of sickness, she had been married. Unfortunately for her husband, with infrequent exceptions, she declined to have sex with him. She had no libido, and would not reach orgasm with him when they did become involved. She was not in love with him, even though he loved her very deeply. Sex for her during this time was, at best, mechanical. However, even without libido, she would regularly masturbate and reach orgasm.
When we first became involved, I was feeling a bit better due to experiencing a partial response to a drug I had recently begun taking. She was dysthymic at the time. We had sex once or twice a day. I had little, if any libido. I guess this sort of thing is not unexpected at the start of a relationship. The thing is, we were good for at least five times a week for over two years. I had lost the improvement fostered by the medication after the first three months, however. Having been severely depressed herself, she did not understand how I could be interested in having sex at all, let alone "perform". Except for the time we were physically involved, I pretty much just sat motionless on the couch with the television on and staring at the floor. I would still look forward to dinner, though. I think one of the keys for me was to not perform at all. It is too easy to get stage-fright. She had no expectations of me, and I had none of myself.
We did have one ace-in-the-hole, however (perhaps a little self-amusement here this time). We were in love. There was no need for anything other than closeness. But we did enjoyed playing in our "sand-box". More often than not, the emotions were more intense than the orgasms. Very often, it was the other way around. However, there was always a caring of the other person and a nurturing of a mutually satisfying experience. There was no such thing as "failure", even if neither of us reached orgasm. Any enjoyment was absolute success. To experience such closeness was absolute success.
All of this being said, I find that it is not necessary for me to be in love to want and enjoy sex, even while being sick. But I will say this. Sex for me is still much more psychological than it is libidinal. For this I feel blessed.
- Scott
Posted by Scott L. Schofield on April 13, 2000, at 10:08:18
In reply to Re: Uprima/Fred, posted by Scott L. Schofield on April 13, 2000, at 7:51:08
Although of Uprima (apomorphine) can be made to induce copulatory behavior when injected into specific areas of the brain in rats, I have not encountered anything to suggest that oral or parenteral administration results in increased libido in humans. It may prove itself to do so, but I don't find enough medical literature on Medline to indicate this with any confidence. The CNN report seems accurate.
Apomorphine has long been recognized as being capable of producing erections. There seem to be two mechanisms involved.
1. Stimulation of the medial preoptic area and/or paraventricular nucleus of the hypothalamus.
- I believe these are the same mechanisms involved in the induction of the nocturnal erections that occur during rapid eye movement sleep (REM).
* The preoptic area may also be involved with libido.2. Increasing the pressure of the "balloon" (corpus cavernosum) located within the penis, causing it to grow in size and stiffness.
Among the more important observations regarding this issue is the lack of the ability of apomorphine to reverse the decrease of libido in mice caused by the loss of testosterone brought about through castration.
------------------------------------------
For Andrew:Apomorphine is one of those drugs that produce opposite effects at low dosages versus high dosages. Apomorphine represents the antithesis of sulpiride and amisulpride. Low dosages produce sedation, while high dosages produce activation and stereotypic behavior. Presynaptic versus postsynaptic regulation.
- Scott
Posted by AndrewB on April 13, 2000, at 10:57:45
In reply to Re: Uprima - libido vs erection, posted by Scott L. Schofield on April 13, 2000, at 10:08:18
Thanks Scott,
Sounds like apomorphine makes one more functional but we're still looking for the love potion that makes the one beside us the object of our desire.
Posted by Sherry on April 13, 2000, at 18:15:22
In reply to Re: Uprima - libido vs erection, posted by Scott L. Schofield on April 13, 2000, at 10:08:18
Scott,
I'm glad you're back!
Sherry> Although of Uprima (apomorphine) can be made to induce copulatory behavior when injected into specific areas of the brain in rats, I have not encountered anything to suggest that oral or parenteral administration results in increased libido in humans. It may prove itself to do so, but I don't find enough medical literature on Medline to indicate this with any confidence. The CNN report seems accurate.
>
> Apomorphine has long been recognized as being capable of producing erections. There seem to be two mechanisms involved.
>
> 1. Stimulation of the medial preoptic area and/or paraventricular nucleus of the hypothalamus.
> - I believe these are the same mechanisms involved in the induction of the nocturnal erections that occur during rapid eye movement sleep (REM).
> * The preoptic area may also be involved with libido.
>
> 2. Increasing the pressure of the "balloon" (corpus cavernosum) located within the penis, causing it to grow in size and stiffness.
>
> Among the more important observations regarding this issue is the lack of the ability of apomorphine to reverse the decrease of libido in mice caused by the loss of testosterone brought about through castration.
>
>
> ------------------------------------------
>
>
> For Andrew:
>
> Apomorphine is one of those drugs that produce opposite effects at low dosages versus high dosages. Apomorphine represents the antithesis of sulpiride and amisulpride. Low dosages produce sedation, while high dosages produce activation and stereotypic behavior. Presynaptic versus postsynaptic regulation.
>
>
> - Scott
Posted by FP on April 13, 2000, at 21:12:39
In reply to Re: Uprima, apomorphine, posted by AndrewB on April 12, 2000, at 9:45:11
I'm dating myself, but William S Burroughs, the junky and "Beat" writer claimed that Apomorphine permanantly cured his craving for heroin. Has anyone ever examined his claim and debunked it, or could there be something to it?
Thanks,
FP
Posted by Fred Potter on April 13, 2000, at 22:35:16
In reply to Re: Uprima, apomorphine - Cam W?, posted by FP on April 13, 2000, at 21:12:39
> I'm dating myself,
I hope you'll both be very happy
>but William S Burroughs, the junky and "Beat" writer claimed that Apomorphine permanantly cured his craving for heroin
But seriously, I wouldn't trust William Burroughs to keep a budgie's pot filled with water
Posted by Cam W. on April 13, 2000, at 23:18:46
In reply to Re: Uprima, apomorphine - Cam W?, posted by FP on April 13, 2000, at 21:12:39
> I'm dating myself, but William S Burroughs, the junky and "Beat" writer claimed that Apomorphine permanantly cured his craving for heroin. Has anyone ever examined his claim and debunked it, or could there be something to it?
>
> Thanks,
> FPFP - I dunno about the apomorphine curing his craving for morphine. For the amount of crap he put into his body, I'm amazed he lived as long as he did. Apomorphine is a dopamine agonist, which perhaps raises dopamine signals (or levels) in the nucleus accumbens (pleasure center thought to be involved in the reinforcement of addictions). Most (if not all) drugs to make you "high" or feel good increase dopamine levels in the nucleus accumbens. When the dopamine levels fall after the drug wears off you crave the increase of dopamine in the nucleus accumbens again, so you take another dose. I think this is how reinforcement works. - Cam W.
P.S. - Burroughs, Kerouac, Cassidy, Ginsberg, et al, were a wacky bunch, weren't they?
Posted by Liz on April 15, 2000, at 12:49:52
In reply to Re: sign me up! (to liz) any opinion Cam?, posted by CarolAnn on April 11, 2000, at 18:05:27
I was cruising through some pharmacy sites this morning and got interested in some of the new drug trials, etc. There is a drug in trials right now from Zonagen, Inc. called Vasofem. (They already market a drug called Vasomax for men which is used treat erectile dysfunction in men.) The oral tablet for women had positive results in pilot studies and is proceeding to phase I trials. The drug is described as "an alpha adrenegic receptor blocker" designed to increase blood flow to the genitals. (generic name: phentolamine mesylate) The initial tests used only post-menopausal women that had complained of vaginal dryness, decreased sexual response, pain w/intercourse and/or anorgasmia. Apparently all the women reported an improved sexual response, enough to encourage further study at least! Also of interest was a summary of the use of Viagra for women. (Pasted quote below) The main point is that research has shown that women who suffer sexual dysfunction due to SSRIs seem to have the best response to Viagra!
"Studies of Viagra in women whose sexual dysfunction may stem from antidepressant use report a more significant effect, however. One study assessed 50 mg Viagra in 9 women who reported sexual dysfunction induced by antidepressant medication, primarily selective serotonin reuptake inhibitors. Patients were instructed to take Viagra approximately 1 hour before sexual activity and were told to increase the dose to 100 mg on the next occasion if they experienced a partial response or a lack of response. The nine patients, all of whom had experienced either anorgasmia or delayed orgasm with or without associated disturbances, reported significant reversal of sexual dysfunction, usually with the first 50 mg dose of Viagra."
Now for the guys: Another drug just got FDA approval and should be available by prescription by mid-summer; its called Androgel and is for a topical application of testosterone to be applied at 24 hour dosing intervals to the upper torso area. Its a colorless get that dries quickly, then is absorbed into the blood stream. I understand that prior to this, men who benefitted from increasing their level of testosterone had previously a choice between deep muscle injections or transdermal patches only. The condition for which it is to be prescribed is called hypogonadism, which I think is another name with perhaps additional symptoms that all result from low levels of testosterone. Anyway, the last sentence of the summary states that virtually all men (w/ lowered testosterone levels) in the study reported an increase in libido, pleasure, ability to maintain erections longer, etc; they also reported significant anti-depressive results from the gel. Are men screened for lower than average testosterone levels as a routine part of their healthcare?? Seems like that would be a place to start for many men w/ a sexual dysfunction. I thought this might have bearing on the libido vs. erection discussion we've been having here....maybe depressed mean with lower libido complaints would benefit even if their testosterone levels are within "normal" ranges.
Just a thought...
PS I'm supposed to be packing our family to catch a plane to Florida tomorrow and here I am, spending hours surfing the web instead...where has all my usual anxiety and panic gone??!! Today I might benefit from no meds! For anyone who might miss me, I'll be severed from my computer for more than a week; I'll look forward to catching up with babblelanders on my return. Liz
*************************************************Your reasoning sounds right to me, liz. Also, the dopamine factor intrigues me. If the drug signals the hypothalmous to release dopamine, I wonder if it could be researched as a possible antidepressant? At any rate, if dopamine affects the genitals the way it affects the brain, well, that's got to be a good thing! CarolAnn
Posted by Scott L. Schofield on April 16, 2000, at 13:59:08
In reply to CarolAnn, et al: an update/Vasomax Vasofem, etc , posted by Liz on April 15, 2000, at 12:49:52
> I was cruising through some pharmacy sites this morning and got interested in some of the new drug trials, etc. There is a drug in trials right now from Zonagen, Inc. called Vasofem. (They already market a drug called Vasomax for men which is used treat erectile dysfunction in men.) The oral tablet for women had positive results in pilot studies and is proceeding to phase I trials. The drug is described as "an alpha adrenegic receptor blocker" designed to increase blood flow to the genitals. (generic name: phentolamine mesylate) The initial tests used only post-menopausal women that had complained of vaginal dryness, decreased sexual response, pain w/intercourse and/or anorgasmia. Apparently all the women reported an improved sexual response, enough to encourage further study at least! Also of interest was a summary of the use of Viagra for women. (Pasted quote below) The main point is that research has shown that women who suffer sexual dysfunction due to SSRIs seem to have the best response to Viagra!
Thanks mucho for this post.
All of this time while watching the Johnny-On-The-Spot commercials, I had no idea that Vasomax was actually phentolamine. This drug is also used as an antihypertensive and is called Regitine. It was at one time available as an oral preparation, but was discontinued in favor of the injectable. It is always available in hospital emergency rooms, and has been considered the treatment of choice for MAO-inhibitor related hypertensive reactions, such as the tyramine "cheese-effect". I've been hoping that an oral form would again appear so as to carry it around with me as a safety precaution. Previously, I had been using nifedipine (Procardia), to be administered sub-lingually (under the tongue, similar to nitroglycerine). I am hoping that Vasomax would be more effective than Procardia.
When I looked into the Vasomax / Vasofem situation, I discovered why there would be "one for him" and "one for her". Vasofem and Vasomax are both preparations of phentolamine. However, Vasofem is a vaginal suppository that is thought may be more effective than the oral preparation for treating the more severe cases of sexual impairment.
Have you seen anything regarding the use of Vasomax in females?
> Your reasoning sounds right to me, liz. Also, the dopamine factor intrigues me. If the drug signals the hypothalmous to release dopamine, I wonder if it could be researched as a possible antidepressant? At any rate, if dopamine affects the genitals the way it affects the brain, well, that's got to be a good thing!
With regard to Uprima (apomorphine), I think somebody at CNN really screwed-up. Uprima does not induce the release of dopamine from the hypothalamus, it induces the release of oxytocin. This oxytocin then travels through the blood-stream to reach its target tissues. The little red line on the CNN graphic should have been labelled "oxytocin", not "dopamine". I believe oxytocin is also responsible for the ejection of milk through the nipple in lactating women (as opposed to lactating men).
Apomorphine is actually fake dopamine. It is similar in this regard to such drugs as bromocryptine (Parlodel), pergolide (Permax), and pramipexole (Mirapex), all of which have been used with reported success for treating depression, along with their primary indications for the treatment of Parkinson's Disease.
- Scott
Posted by boB on April 16, 2000, at 21:14:38
In reply to Re:to liz - serotonin and dopamine - musings, posted by Cam W. on April 11, 2000, at 23:19:39
this is a new one on me. ... serotinin and dopamine interact in opposition?
i have heard about norepinephrine interacting more or less in opposition to serotonin, and acetecholine acting in opposition to aminergins...
I'm not very well grounded in neurochemistry, but i can struggle through an article on the subject if you know where to send me. How do serotonin and dopamine interact in opposition
Posted by Cam W. on April 16, 2000, at 22:52:07
In reply to Cam - serotonin and dopamine opposition, posted by boB on April 16, 2000, at 21:14:38
boB - I do believe that dopamine and serotonin antagonize each others actions. I can see in my mind's eye the notes that I took at a schizophrenia conference a few years ago. The notes are in my files at work. I will pull them out for a clearer definition than in the example I am going to give you below.An example of this in action is with the atypical antipsychotics (eg Clozaril, Zyprexa, Risperdal, etc.). All of these have a greater affinity for blocking serotonin-2A (5HT-2A) receptors than dopamine-D2 (D2) receptors, but still have action at the dopamine receptors. The mechanism of action of the traditional neuroleptics (eg Haldol, Largacil, Mellaril, etc.) is thought to be dopamine-D2 blockade.
5HT-2A receptors are concentrated in the reticular activating system (raphe nuclei) and in limbic regions. D2 receptors are concentrated in the limbic system and in the prefrontal cortex. So by blocking D2 receptors in the prefrontal cortex you are relieving the postive symptoms of schizophrenia. But (here is where the opposition occurs) by blocking 5HT-2A receptors in the limbic system and sparing dopamine transmission (due to receptor affinity differences) you do not get the movement disorders from the atypical antipsychotics, as you would with the traditional antipsychotics. The 5-HT-2A blockade in the limbic system increase the flow of dopamine, but in the prefrontal cortex (where there is a lack of 5HT-2A receptors) the D2 blockade acts upon the positive symptoms of schizophrenia.
If I remember (and can find my notes) I will post a more insightful answer tomarrow. I will also give you the reference so you can look up the article from where I got this as well. - Cam W.
Posted by Cam W. on April 16, 2000, at 23:28:50
In reply to Re: Cam - serotonin and dopamine opposition, posted by Cam W. on April 16, 2000, at 22:52:07
boB - Well, I'll be horse-whipped! Never underestimate the power of the Google Search Engine. I found the article right away in The American Journal of Psychiatry. If you have access to a university library, look up the following article. It is very interesting (they want you to pay for an on-line subscription). The abstract does mention the serotonin/dopamine interaction though (see FINDINGS).
http://ajp.psychiatryonline.org/cgi/content/abstract/153/4/466
S.Kapur and G.Remington -
"Serotonin-dopamine interaction and its relevance to schizophrenia."Happy reading - Cam W.
Posted by boB on April 17, 2000, at 17:42:32
In reply to Re: Cam - serotonin and dopamine opposition, posted by Cam W. on April 16, 2000, at 23:28:50
> Cam - it might be a few weeks until I can get hold of that entire article. I think I get a sense of what you are saying about working in opposition, but I don't get the sense you are saying high serotinin activity neccesarily means low dopamine activity and vice versa. Am I on the right track?
Posted by Cam W. on April 17, 2000, at 18:44:16
In reply to Re: Cam - serotonin and dopamine opposition, posted by boB on April 17, 2000, at 17:42:32
boB - Yes I blieve that you are on the right track. I don't think that a high serotonin level means that there is a low dopamine levels or vice versa. I think it is more of a situation where one neurotransmitter 'influences' the other. I believe that there could be situations where both are high and both are low. These two neurotransmitter do not work in a vacuum and several of the other neurotransmitters (eg glutamate, GABA, norepinephrine, peptides, endorphins, etc.) also play a role in serotonin and dopamine levels. Also genetics would have a role, as would the endocrine system. I do not have a total grasp on this concept, so I cannot be sure of exactly how it works. Sincerely - Cam W.
Posted by boB on April 17, 2000, at 20:48:41
In reply to Re: Cam - serotonin and dopamine opposition, posted by Cam W. on April 17, 2000, at 18:44:16
thanks, Cam,
Maybe you can help me with this one though - doesn't a lot of sensory processing and learning have to do with an inititial jolt of norepenephrine, which is somehow ...what is the word?. it - the norepenephrine networks - continue to increase in amplitude or something until a familiar network - like a familiar concept or experience - allows a reinforcing neurotransmitter to establish a stable .. uh a stable uh .. thought?
i cant remember where I got that idea but I know I'm not smart enough to make it up. I don't have ready access to the libraries where I was boning up on neurochemistry, so I can't recall if I synthesized the idea from several sources or if that is the way a very well informed brain scientist explained it in a very expensive book.
i am much more confident of my understanding of acetecholine dominating sleep and aminergins (?) such as nore., dopa., and serotonin dominating waking states. I could find at least two reliable books about that, real easy.
Any clues?
- boB
Posted by Scott L. Schofield on April 17, 2000, at 20:54:18
In reply to Re: Cam - serotonin and dopamine opposition, posted by Cam W. on April 17, 2000, at 18:44:16
I think it is time to think of the brain as a network of different railroads, each of which using a different fuel to power their trains as they deliver the mail.
Things make a lot more sense this way.
- Scott
Posted by Cam W. on April 17, 2000, at 21:49:55
In reply to Re: Cam - serotonin and dopamine opposition, posted by boB on April 17, 2000, at 20:48:41
boB - I am woefully deficient in my understanding of the mechanisms behind how working memory becomes long term memory. I think it has more to do with the NMDA (N-methyl-D-aspartate?) receptor complex. These receptor complexes have a near saturation of glycine attached to them (a basal glycine level) and are stimulated by the neurotransmitter glutamate. I am not sure whether norepinephrine triggers (or amplifies) the process in which the NMDA complex 'lays down' the neural circuitry for long term memory, but I'll bet it involves a number of neurotransmitters. (Actually I am not positive NMDA is involved, but I have a nagging feeling it is - I need my file cabinet at home rather than at work).Like yourself, I am piecing together this information from a number of different articles and I am still missing several of the puzzle pieces. Sorry that I cannot help more than this. If I remember which file I put these articles (either in neuroanatomy or antipsychotics or schizophrenia or consciousness) and can find them, I will try to get back to you on this tomarrow. - Cam W.
Posted by Zeke on April 18, 2000, at 15:13:52
In reply to Re: Cam - serotonin and dopamine opposition, posted by Cam W. on April 17, 2000, at 21:49:55
Serotonin and dopamine opposition -- well yes and no...
The actions of neurotransmitters are complex. Saying DA and 5HT antagonize one another (or one another's actions) is best viewed as a generalization. Many subcortical circuits use serotonin at one junction and dopamine at another.
Consider also that dopamine and serotonin also act to oppose (inhibit) themselves, eg, through autoreceptors. (Or through action: ACh 'opposes' its actions in the PNS.)
Other considerations:
Be careful generalizing from results of studies in persons with abnormal brain chemistry like schizophrenia. (Does a non-schizophrenic brain act like a schizophrenic brain? In schizophrenia, some dopamine circuits are hyperactive, some hypoactive.)
Be careful generalizing transmitter function with higher level functions such as mood; Different dopamine agonists have different effects for example on mood: amphetamine tends to improve mood while levodopa tends to lower mood.
IMHO, much is to be learned from the happenings inside neurons. Along with genetics this will involve neurosteroids etc. This seems to me why antidepressants have an effective (affective) time lag whis their synaptic action is immediate.
Another complicating issue is the recent finding that transmission can occur electrically without any neurotransmitter (in certain processes).
Lastly, if one transmitter inhibits the other, we can say 'oppose' or we can say 'modulate'. I tend to see DA/5HT more in the 'modulate' sense.
Posted by Cam W. on April 18, 2000, at 23:46:58
In reply to Re: Cam - serotonin and dopamine opposition, posted by boB on April 17, 2000, at 20:48:41
Zeke and boB - I have tried twice to post a very long answer as a follow-up to Zeke's thread. I have some very complicated info on neurotransmitter interactions, but after 1.5h of trying to post a synopsis of the studies, I will just give you the bibliography. The answers I was going to give were too involved for this site and taken out of context of the original articles may have made things more confusing.Zeke is correct about using modulating, rather than opposition when taking of the interactions between dopamine and serotonin. Stimulation of different serotonin receptor subtypes will either increase or decrease dopamine synthesis and release in different parts of the brain.
The good articles I have found on the interactions between neurotransmitters are:
Murphy D et al. Brain serotonin neurotransmission: an overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs, J Clin Psychiatry, 1998; 59[suppl 15]: 4- 12.
(yes, that is the title)Kapur S & Remington G. Serotonin-dopamine interaction and its relevance to schizophrenia, Am J Psychiatry, April, 1996; 153(4): 466-476.
Richelson E. Receptor pharmacology of neuroleptics: relation to clinical effects, J Clin Psychiatry, 1999; 60[suppl 10] : 5-14.
Bonhomme N. Involvement of serotonin and dopamine in the mechanism of action of novel antidepressant drugs: a review, J Clin Psychopharmacol; 1998; 18(6): 447-454.
These papers should give you a descent basis for some of the neurotransmitter function. I still haven't totally grasped the concepts, yet. I think I need a few more papers and a lot more time. - Cam W.
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