![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 40 to 64 of 98. Go back in thread:
Posted by CrAzYmEd on May 24, 2010, at 22:42:09
In reply to Re: Lisuride Experiences: Mixed Bag, Not The New Cool, posted by CrAzYmEd on May 23, 2010, at 18:19:43
This study found lisuride effective for 80% of the patients, but then again this wasnt for regular depression but depression after a stroke.
[Therapeutic effect of lisuride maleate on post-stroke depression]
[Article in Japanese]Hougaku H, Matsumoto M, Hata R, Handa N, Imaizumi M, Sugitani Y, Yoneda S, Etani H, Sueyoshi K, Kusunoki M, et al.
First Department of Medicine, Osaka University Medical School.
Abstract
Twenty post-stroke depressive patients who obtained more than 11 points on Self-Rating Questionnaire for Depression, were treated with 0.075 mg/day lisuride maleate for 12 weeks. The drug effect on depression was evaluated quantitatively by the Hamilton Rating Scale for Depression. The relationships between brain CT or MRI and SRQ-D score were investigated in 24 subjects. More than 80% of post-stroke depressive patients improved after lisuride maleate treatment for 8 or 12 weeks. In particular, depressed mood, hypobulia, sleep disturbance, anxiety, etc. were significantly improved compared to the baseline condition. As for the relationships with CT and/or MRI findings, the group with moderate to severe brain atrophy had a significantly higher grade of depressive state than those without.
Posted by linkadge on May 24, 2010, at 22:42:10
In reply to Lisuride Experiences: Mixed Bag, Not The New Cool, posted by Brainbeard on May 23, 2010, at 18:13:42
I don't buy the notion that dopamine agonists decrease dopamine function (overall). If this were true, why are they effective (long term) for parkinsons disase?
Some agonists, like mirapex, have preferential effects on the presynaptic dopamine receptor. Over time, the drug might well downregulate the dopamine autoreceptor and thus enhance neurotransmission.
Linkadge
Posted by Brainbeard on May 24, 2010, at 22:43:11
In reply to , posted by on December 31, 1969, at 18:00:00
> I don't buy the notion that dopamine agonists decrease dopamine function (overall). If this were true, why are they effective (long term) for parkinsons disase?
You can only expect them to, since they mimick dopamine, binding to dopamine receptors, pushing the real thing out of the way. This is supposedly the reason why non-ergoline dopamine agonists cause sleep attacks.
I believe that OCD is a form of hyperdopaminergic activity, and that SSRI's work for OCD because of their anti-dopaminergic properties. But the overall story is so complex, I readily admit that I only understand a tiny bit of the whole picture.
Posted by CrAzYmEd on May 24, 2010, at 22:44:00
In reply to , posted by on December 31, 1969, at 18:00:00
Personally i beleive that the low dopamine binding in OCD comes from hyperactive glutamate activity (just as glutamate hyperactivity seems to cause low dopamine binding in ALS).
--------------------------------------
Decreased striatal dopamine-receptor binding in sporadic ALS: Glutamate hyperactivity?O. J. M. Vogels, MD, PhD, W. J. G. Oyen, MD, PhD, B. G. M. van Engelen, MD, PhD, G. W. A. M. Padberg, MD, PhD and M. W. I. M. Horstink, MD, PhD
From the Departments of Neurology (Drs. Vogels, van Engelen, Padberg, and Horstink) and Nuclear Medicine (Dr. Oyen), University Hospital Nijmegen, the Netherlands.Address correspondence and reprint requests to Dr. O.J.M. Vogels, Department of Neurology, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
The pathogenesis of ALS may be related to increased glutamatergic excitotoxicity. The striatum receives massive glutamatergic input. Animal studies suggest that glutamate decreases striatal D2-receptor synthesis. In drug-naïve, sporadic ALS patients we demonstrated decreased striatal D2-receptor binding in vivo that could be partially reversed by the glutamatergic transmission blocker riluzole. Our findings support the glutamatergic excitotoxicity hypothesis in sporadic ALS.
--------------------------------------------Memantine has been shown effective for OCD (it did wonders for wine) while it hasnt got any anti dopaminergic activity, instead it can upregulates dopamine receptors (altough no idea how significant this is in therapeutic relevant doses) and has dopamine agonist properties itself.
But yeah its really complex, and this is my own little theory :p, but i dont buy the too much dopamine theory.
Interesting discussion besides:p.
Posted by CrAzYmEd on May 24, 2010, at 22:44:00
In reply to Lisuride, incredible potential, posted by CrAzYmEd on May 23, 2010, at 7:18:25
Srry if i sound like a found a new miracle, i'm just interested in lisuride and think it can be a interesting med.
Posted by Brainbeard on May 24, 2010, at 22:44:00
In reply to Not wonder med, just interested in it., posted by CrAzYmEd on May 24, 2010, at 6:11:45
Interesting discussion indeed. Wouldn't have been possible had we agreed. ;)
You got me interested in lisuride too, I just don't feel attracted to the initial nausea it is likely to produce.
On the other hand, how cool it would be to be on a chemical sister of LSD?!
And reducing prolactin levels seems like a good idea when on antidepressants and antipsychotics that can cause hyperprolactinemia, like myself.
Posted by CrAzYmEd on May 24, 2010, at 22:44:00
In reply to Disagreeing, The Holy Grail And Man-Boobs, posted by Brainbeard on May 24, 2010, at 10:50:08
I wonder how this one would work with amisulpiride or sulpiride. With the combination we wouldnt have to wait for the autoreceptors to downregulate as it would keep the lisuride off the autoreceptors so it can go directly to the postsynaptics. (A friend of me has good succes with the sulpiride/pramipexole combo).
Also maybe the amisulpiride would block some of lisuride's agonism in the puking center, while lisuride blocks the huge prolacting increase by amisulpiride.
This would only work if ami's affinities for the presynaptic receptors is higher then lisuride, so lisuride doesnt knock it off the autoreceptors. But it appears to work with pramipexdole.
Just an idea.
I will try to get ahold of lisuride myself, would be awesome if i found a open minded doc so it would be insured by the goverment:p.
Besides, props to you man, ive seen some of your old posts, very good information and contributions you post here.
Posted by Brainbeard on May 24, 2010, at 22:44:43
In reply to , posted by on December 31, 1969, at 18:00:00
Posted by Brainbeard on May 25, 2010, at 15:45:51
In reply to Lisuride, incredible potential, posted by CrAzYmEd on May 24, 2010, at 22:41:53
http://www.freepatentsonline.com/4045562.html:
'Lisuride and the physiologically acceptable salts thereof are psychic energizers without simultaneously exhibiting the disadvantages (stimulating effect and development of dependency) of the phenylethylamine derivatives. There is a significant therapeutic effect in so-called neurasthenic symptomatology, mainly in the following symptoms: loss of interest, loss of drive and activity, loss of energy and functional capacity, loss of concentration and learning ability. They possess surprisingly high compatibility even at the large doses of this invention and there is no development of dependency, even after long-term administration at these large dosages.
The spectrum of psychic energizer activity, discovered with the aid of the quantitative Pharmaco-EEG, (T. M. Itil; Diseases of the Nervous System 8 (1972) 8) is novel and has not been found for another drug. The objective results are laid down in parameters of the EEG's analyzed by computer and the spectrum of effectiveness is characterized by a decrease of the delta and theta waves, and increase in the alpha and slow beta waves, as well as a decrease of the superimposed fast waves (up to 100/second). These phenomena affecting the physiology of the brain point to certain stimulating and simultaneously inhibiting effects exerted by lisuride. Accordingly, lisuride has a clinical spectrum of activity which can be called "Energizer Anxiolytic" (T. M. Itil et al., Int. J. Clin. Pharmacol. Ther. & Toxicol. 10[ 1974] 143).'
Posted by CrAzYmEd on May 25, 2010, at 17:04:05
In reply to Lisuride, The Anxiolytic Energizer?, posted by Brainbeard on May 25, 2010, at 15:45:51
That is really interesting! Good find.
Posted by Brainbeard on May 26, 2010, at 5:55:33
In reply to Re: Lisuride, The Anxiolytic Energizer?, posted by CrAzYmEd on May 25, 2010, at 17:04:05
A pity this stuff has such a short half-life. That'll make titration even more difficult.
Posted by CrAzYmEd on May 26, 2010, at 6:50:24
In reply to Re: Lisuride, The Anxiolytic Energizer?, posted by Brainbeard on May 26, 2010, at 5:55:33
But its possible to make a time released preparation. I forgot how to do it again tough, will try to find it.
Posted by Conundrum on May 27, 2010, at 21:02:04
In reply to Let's Have Dopamine Pie For Lunch, posted by Brainbeard on May 24, 2010, at 22:42:05
If you do some searching around the web you can find that 5 HT2A agonism by LSD promotes learning in rats and 5 HT2A antagonism deters learning. Maybe not in humans though. I think in humans its more trouble than its worth. Seems to cause sexual side effects and what fun is that?
Posted by Conundrum on May 27, 2010, at 21:18:00
In reply to Re: Let's Have Dopamine Pie For Lunch, posted by linkadge on May 24, 2010, at 22:42:07
I didn't know that. I guess anything is possible. How would one know if they're anhedonia is caused by too little or too much dopamine. Is there any differentiation in other symptoms.
I've tried some dopaminergic supplements and drugs like wellbutrin and ritalin which never did anything for me. Also before the anhedonia got worse I did have some paranoia like listening to conspiracy theorists and into spirituality, which is now gone but I can think more logically. Interestingly these feelings of spirituality and interconnectedness of all things started after stopping prozac, so it seems like a dopaminergic rebound. Then after taking ginkgo for two years and stopping all these feelings disappeared good and bad.
I feel as if my dopamine or noradrenaline dropped, but is it possible it went too high? I am being treated for slightly elevated blood pressure, but that might just be because I'm slightly overweight. I guess the only way to find out would be to try an antipsychotic med. I'm still leaning towards low catecholamines though.
Posted by CrAzYmEd on May 28, 2010, at 6:14:47
In reply to Re: Let's Have Dopamine Pie For Lunch » Brainbeard, posted by Conundrum on May 27, 2010, at 21:02:04
What causes sexual side effects? Lisuride will have PRO sexual effects like all other dopamine agonists by lowering prolactin.
Yes, LSD can increase learning but it does alot more then just 5HT2A agonism (its binding is very simular to lisuride).
LSD: 4.00 5ht1b, 3.77 5ht7, 3.75 5ht6, 3.73 5ht1a, 3.70 5ht1d, 3.64 5ht5a, 3.54 5ht2a, 3.16 D3, 3.11 5ht2b, 3.11 5ht2c, 2.93 Alpha2A, 2.62 5ht1e, 2.55 D2, 2.39 D4, 2.34 D1, 2.05 D5, 1.54 Alpha1A, 1.40 H1, 1.39 Beta1, 1.05 Beta2, 0.65 Alpha1B; 0.00: KOR, DOR, DAT, SERT, MOR, NET; ND: Sigma2, Alpha2B, Alpha2C, Imidazoline1, M1, M2, M3, M4, M5, Sigma1, H2, CB2, CB1, Ca+Channel, NMDA
(4 is best affinity, and under 2 not significant).
Posted by CrAzYmEd on May 28, 2010, at 6:18:27
In reply to Too much dopamine causes anhedonia? » linkadge, posted by Conundrum on May 27, 2010, at 21:18:00
Prozac wont cause a dopamine rebound as it raises dopamine itself: (It can really be anything, its impossible to point a effect of the withdrawal to any receptor)
---------------------------------
http://www.ncbi.nlm.nih.gov/pubmed/15741747
"Twelve patients affected by major depression received a single oral dose of fluoxetine in the morning, 5 mg in the first 5 days, 10 mg from the 6th to the 10th day and 20 mg from the 11th to the 40th day. Twelve healthy subjects received a placebo under identical testing procedures. Blood samples were collected at baseline and 7, 10 and 24 h after drug administration on the 1st day of fluoxetine administration at a dose of 5 mg, and on the 1st and the 30th day of fluoxetine administration at a dose of 20 mg (days 11 and 40 of treatment, respectively). We found that plasma norepinephrine, epinephrine and dopamine levels significantly increased after acute and chronic treatment (p < 0.001), reaching the highest concentrations on the last day. No significant changes of these parameters were observed in control patients."
-------------------------------------
I highly suggest against antipyschotics for the treatment of anxiety or depression, they should only be used to treat psychotic disorders. The risk of tardive dyskinesia and metabolic problems are not wort it.
Posted by Conundrum on May 28, 2010, at 9:23:31
In reply to Re: Too much dopamine causes anhedonia?, posted by CrAzYmEd on May 28, 2010, at 6:18:27
I think that prozac would still have a suppressive effect on dopamine in some areas of the brain though. I believe this is why it is effective in the treatment of OCD.
Interestingly the first 2 years off prozac my memory was bad so I took ginkgo for those first two years. It had a very powerful effect on me and if I took to much I had much more physical endurance and couldn't sleep. Like too much oxygen. Anyway a month after stopping it all the spiritual and loving feelings went away and I was hit with even worse anhedonia. At least then I was able to rid myself of those things. I was never into astrology or numerology before that or believed in conspiracies. I became better at using the logical part of my mind and eliminating unhelpful believes. So I guess in a way its has been helpful. I have no idea the physiology behind any of that though.
I have a similar feeling about atypical APs but it seems like psychiatrists are more comfortable prescribing them than tricyclics!
Posted by CrAzYmEd on May 28, 2010, at 9:47:04
In reply to Re: Too much dopamine causes anhedonia? » CrAzYmEd, posted by Conundrum on May 28, 2010, at 9:23:31
I dont buy the high dopamine OCD theory, this theory only comes from the low D2 bindin in humans and the fact that antipsychotics work for it.
However, there is loads of evidence for glutamate hyperactivity in OCD, glutamate downregulates D2, wich could be the cause of low D2 binding.
Also a good friend of me had moderate succes with pramipexole for OCD (and this isnt due to reduced dopamine, as he's autoreceptors are fully downregulated by now).
While i havent tried a dopamine agonist, i know that drugs that increase dopamine and NMDA antagonists are highly effective for my OCD.
Memantine, is a D2 agonist besides its nmda antagonism and has been found effective for OCD, prozac wich increases dopamine has been found effective for OCD too.
Posted by Brainbeard on May 28, 2010, at 15:17:55
In reply to Lisuride, incredible potential, posted by CrAzYmEd on May 24, 2010, at 22:41:53
I found a very interesting article on the interplay between unspecific 5HT activation and 5HT2A-activation or blocking as well as 5HT2C-agonism or antagonism:
http://www.nature.com/npp/journal/v28/n2/full/1300057a.html
There is a consesnus based on clinical evidence that 5HT2A-agonism opposes the beneficial effects of unspecific 5HT-activation through serotonin reuptake inhibition (SRI). Thus, 5HT2A-antagonists have been shown to fasten and boost the efficacy of SSRI's. The indirect agonism of 5HT2A receptors by SSRI's is a mechanism that inhibits c.q. defeats the benefits of agonism of other 5HT receptors, probably most notably 5HT1A-receptors.
5HT2A-agonism leads to sexual dysfunction and anxious moods.
In the article mentioned above it's also stated that 5HT2A-agonism promotes glutamate release.5HT2A and 5HT2C receptors have opposing functions in several ways. 5HT2C-agonism has shown to have antidepressant potential. It increases exuality. 5HT2C-antagonism may inhibit the benefits of 5HT2A-antagonism! This is an interesting find since most 5HT2A-antagonists are also 5HT2C-antagonists at least to some degree.
I have become convinced that several of the start-up effects that I typically experience when starting escitalopram are due to 5HT2C-agonism. The first days on escitalopram, and after raising the dose, I have a feeling that resembles my experiences on magic mushrooms. Time is being stretched out immensely: hours last extremely long and I can't believe what the clock is telling me. My appetite is suppressed - a known effect of 5HT2C-agonism. I feel euphoric and hyperseuxal.This must be 5HT2C-agonism!
If lisuride would be an ideal drug, it would at least have to be a 5HT2A-ANTAGONIST and a 5HT2C-agonist. Since it appears to be a stronger 5HT2A-agonist than a 5HT2C-agonist, these two mechanisms will downplay each other's benefits.
Fluoxetine/Prozac, by the way, of course has antidopaminergic properties, like any SSRI. Serotonin puts a brake on dopamine, to put it simply. Prozac causes sexual dysfunction like any other SSRI. It elevates prolactin levels like any other SSRI, which is also an antidopaminergic feature.
Posted by Brainbeard on May 28, 2010, at 15:37:58
In reply to 5HT2A-antagonism + 5HT2C-agonism Would Be Ideal, posted by Brainbeard on May 28, 2010, at 15:17:55
Quotes from mentioned article:
'Interactions have also been observed between 5-HT2A and 5-HT2C receptors at a behavioral level. Opposing effects exist for 5-HT2A and 5-HT2C receptors in modulating hyperlocomotion induced in mice by noncompetitive N-methyl-d-aspartate (NMDA) antagonists (Martin et al, 1997). A recent study has found clear evidence supporting opposing effects of 5-HT2A and 5-HT2C receptors in modulating head shakes in rats (Vickers et al, 2001). Activation of 5-HT2A and 5-HT2C receptors also leads to opposing effects on sexual function in rodents (Berendsen et al, 1990), in a manner suggesting that activation of 5-HT2A receptors could be responsible for the sexual side effects of SSRIs. DRL 72-s behavior also appears to involve reciprocal interactions between 5-HT2A and 5-HT2C receptors, since 5-HT2C agonists, similar to 5-HT2A antagonists, exert antidepressant-like actions in rats performing under this operant paradigm (Marek and Seiden, 1988; Martin et al, 1998; Marek et al, 2001a). In a similar vein, blockade of 5-HT2C receptors may attenuate the antidepressant-like effects observed on the DRL 72-s schedule following administration of drugs that block 5-HT2A receptors (Marek and Seiden, 1994).'
.....
'Activation of 5-HT2C receptors appears to cause effects that functionally oppose the effects resulting from activation of 5-HT2A receptors (see above). These two receptors are differentially regulated by antidepressants in a manner that could have clinical relevance (Berendsen and Broekkamp, 1991). Other preclinical work in rodents has found that 5-HT2C agonists have antidepressant-like action in the forced swim test, the olfactory bulbectomy model, and the DRL 72-s schedule (Martin et al, 1998; Cryan and Lucki, 2000). Moreover, a polymorphism for the 5-HT2C receptor has been linked to mood disorders (Lerer et al, 2001). This might result in an alteration of 5-HT2C function independent of receptor abundance. Alterations in RNA editing of 5-HT2C receptors has been reported in suicide victims (Niswender et al, 2001). Thus, simultaneous blockade of 5-HT2A receptors and activation of 5-HT2C receptors could result in an improved therapeutic benefit over either of these actions in isolation.'
Posted by CrAzYmEd on May 28, 2010, at 15:57:35
In reply to 5HT2A-antagonism + 5HT2C-agonism Would Be Ideal, posted by Brainbeard on May 28, 2010, at 15:17:55
"Fluoxetine/Prozac, by the way, of course has antidopaminergic properties, like any SSRI. Serotonin puts a brake on dopamine, to put it simply. Prozac causes sexual dysfunction like any other SSRI. It elevates prolactin levels like any other SSRI, which is also an antidopaminergic feature."
But whats the end result? I dont say there arent any anti dopaminergic propertie's, but its 5HT2C antagonism may counteract any anti dopaminergic activity, so in the end its not anti dopaminergic anymore.
Like the study i posted points toward INCREASED dopamine and not reduced.
Posted by CrAzYmEd on May 28, 2010, at 16:22:21
In reply to 5HT2A-antagonism + 5HT2C-agonism Would Be Ideal, posted by Brainbeard on May 28, 2010, at 15:17:55
"There is a consesnus based on clinical evidence that 5HT2A-agonism opposes the beneficial effects of unspecific 5HT-activation through serotonin reuptake inhibition (SRI)."
The opposing powers! There's allways a bad boy around counteracting the benefits of mr good guy, but then again there's mr good guy counteracting the problems the bad boys are causing!
It seems that when other receptors are either activated or inhibited, the effects of agonism of a differend receptor could be completely differend, like you say that 5HT2C antagonism could counteract the benefits of 5HT2A antagonism. So id say it depends on the situation wheter 5HT2A antagonism is good.
About your experience with SSRI's, 5HT2A agonism plays a big role in the mushroom experience too , so i wouldnt only point to 5HT2C agonism, its the whole mix, and suprisingly the pharmacological profile of mushrooms is very simular to that of lisuride except that mushrooms seem to be a strong D1 agonist too.
I'm still convinced that 5HT2A agonism is better then 5HT2A antagonism tough (in some situations atleast), 5HT2A can facilate dopamine release togheter with the 5-HT1A, 5-HT1B, 5-HT3 and 5-HT4 receptors. 5HT2A is also crucial for the dopamine release by amphetamine's and opiates while 5HT2C can inhibit it (its a weird one)
-------------------------------------
Pharmacol Ther. 2007 Feb;113(2):296-320. Epub 2006 Oct 17.
Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission.
Alex KD, Pehek EA.Department of Neurosciences, Case Western Reserve School of Medicine, Cleveland, OH 44106, USA.
Abstract
The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all 3 major dopaminergic pathways. There are at least fourteen 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.--------------------------------
I should take a look at the full paper of that study.
Will take a better look at your post tomorrow, have to get up early today, morgen weer gaan werken:p.
Posted by CrAzYmEd on May 28, 2010, at 16:29:00
In reply to Re: 5HT2A-antagonism + 5HT2C-agonism Would Be Ideal, posted by CrAzYmEd on May 28, 2010, at 16:22:21
But this is about fear tough, not depression, but werent SSRI's also capable of increasing depression when starting the treatment, dont exactly remember, i actually tought that this was also due to 5HT2C agonism, but 5HT2C doesnt appear to be the big gangster as i first tought.
Acute SSRIs Increase Conditioned Fear Expression: Blockade with a 5-HT2C Receptor Antagonist
N.S. Burghardt,1 D.E.A. Bush,1 B.S. McEwen,2 and J.E. LeDoux1Background
SSRIs effectively treat various anxiety disorders, although symptoms of anxiety are often exacerbated during early stages of treatment. We previously reported that acute treatment with the SSRI citalopram enhances the acquisition of auditory fear conditioning, which is consistent with the initial anxiogenic effects reported clinically. Here, we extend our findings by assessing the effects of acute SSRI treatment on the expression of previously acquired conditioned fear.Results
A single pre-testing injection of the SSRIs citalopram or fluoxetine significantly increased fear expression. There was no effect of the antidepressant tianeptine, or the norepinephrine reuptake inhibitor, tomoxetine, indicating that this effect is specific to SSRIs. The SSRI induced enhancement in fear expression was not blocked by tropisetron, a 5-HT3 receptor antagonist, but was blocked by SB 242084, a specific 5-HT2C receptor antagonist.Conclusions
Enhanced activation of 5-HT2C receptors may be a mechanism for the anxiogenic effects of SSRIs observed initially during treatment.
Posted by Brainbeard on May 29, 2010, at 7:37:55
In reply to Re: 5HT2A-antagonism + 5HT2C-agonism Would Be Ideal, posted by CrAzYmEd on May 28, 2010, at 15:57:35
> "Fluoxetine/Prozac, by the way, of course has antidopaminergic properties, like any SSRI. Serotonin puts a brake on dopamine, to put it simply. Prozac causes sexual dysfunction like any other SSRI. It elevates prolactin levels like any other SSRI, which is also an antidopaminergic feature."
>
> But whats the end result? I dont say there arent any anti dopaminergic propertie's, but its 5HT2C antagonism may counteract any anti dopaminergic activity, so in the end its not anti dopaminergic anymore.
>
> Like the study i posted points toward INCREASED dopamine and not reduced.Those studies only show short-term effects. Increase in certain area's of the brain doesn't mean overall increase either.
In fact, 5HT2C-antagonism and SRI are opposing mechanisms. Only in lower doses Prozac's 5HT2C-antagonism may dominate, because of the non-linear dose/response relationship for 5HT2C-antagonism, i.e. only a little is enough for significant effects. On higher (therapeutical) doses however, the benefits of 5HT2C-antagonism will be mostly blown away by indirect 5HT2C-agonism. In accordance with this prediction is the fact that high doses of Prozac are used as an anti-bulimia agent, i.e. to suppress appetite. 5HT2C-antagonism INCREASES appetite, while 5HT2C-agonism suppresses it.
There is a very informative study on the web about Prozac's 5HT2C-antagonism in relation to its SRI here: http://www.pnas.org/content/94/5/2036.full.pdf. Please read the part between starts (***).
A quote: 'So far, the therapeutic effects of fluoxetine have been attributed primarily to its inhibition of 5HT transporters. Interestingly, it has been shown that the therapeutic plasma concentration of fluoxetine is in the micromolar range, and our studies show that, at this concentration range, fluoxetine can potently inhibit the membrane current responses mediated by 5HT2C receptors. Moreover, the affinity of fluoxetine for 5HT2C receptors (Ki 5 65 nM) is close to its affinity for 5HT transporters (Ki 5 33 nM) (29), which is also well below the therapeutic plasma concentration of fluoxetine. Thus, some therapeutic effects of fluoxetine may be a consequence of blocking both 5HT transporters and 5HT2C receptors. ***It should be noted that the blockage of 5HT transporters and that of 5HT2C receptors would have opposing actions on serotonergic synaptic transmission.*** (.....) Because of the highly nonlinear dose/response relationship of 5HT2C receptors the blockage of even a small number of receptors in a cell would lead to very profound changes (.....)'.
You seem to jump to overstatements like 'its 5HT2C antagonism may counteract any anti dopaminergic activity, so in the end its not anti dopaminergic anymore.' That's about as unfounded a prediction as saying that lisuride's 5HT1A-agonism will completely counter its anxiogenic properties. Lisuride probably fosters OCD.
If you look at this interesting study on lisuride that I found on Erowid: http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=3705; you see that lisuride induced stereotypical behaviour in rats as well as intensive mounting, i.e. male sexual behaviour. Stereotypical behaviour indicates the potential to exacerbate or induce obsessive compulsive behaviour. And increased libido is not always fun, althoug the accompanying photo of one female rat mounting the other is rather funny.
Anyhow, 5HT2A-agonism inhibits the benefits of both 5HT1A- and 5HT2C-agonism. That's a clinical finding. So if you want to simplify it into good guy vs. bad guy terminology, lisuride does have a bad guy on board, and it's called 5HT2A-agonism. No matter what good things 5HT2A-agonism may do on its own, it's bad news for 5HT1A- and 5HT2C-agonism.
Posted by CrAzYmEd on May 29, 2010, at 8:16:34
In reply to Prozac, 5HT2C And The Trojan Horse In Lisuride, posted by Brainbeard on May 29, 2010, at 7:37:55
"You seem to jump to overstatements like 'its 5HT2C antagonism may counteract any anti dopaminergic activity, so in the end its not anti dopaminergic anymore.' That's about as unfounded a prediction as saying that lisuride's 5HT1A-agonism will completely counter its anxiogenic properties. Lisuride probably fosters OCD."
But its not a overstatement as according to this study it DOES increase dopamine, i never made that conclusion just because prozac is a 5HT2C antagonist, i only made that conclusion on the END result.
-----------------------------------------
http://www.ncbi.nlm.nih.gov/pubmed/15741747
"Twelve patients affected by major depression received a single oral dose of fluoxetine in the morning, 5 mg in the first 5 days, 10 mg from the 6th to the 10th day and 20 mg from the 11th to the 40th day. Twelve healthy subjects received a placebo under identical testing procedures. Blood samples were collected at baseline and 7, 10 and 24 h after drug administration on the 1st day of fluoxetine administration at a dose of 5 mg, and on the 1st and the 30th day of fluoxetine administration at a dose of 20 mg (days 11 and 40 of treatment, respectively). We found that plasma norepinephrine, epinephrine and dopamine levels significantly increased after acute and chronic treatment (p < 0.001), reaching the highest concentrations on the last day. No significant changes of these parameters were observed in control patients."
------------------------------------------
Plasma increased of dopamine are increased, after acute and chronic dosing, so unless the dopamine increase comes from something else then 5HT2C antagonism, the serotonine does NOT counteract the 5HT2C antagonism.
Go forward in thread:
Psycho-Babble Neurotransmitters | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.