![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 24 to 48 of 98. Go back in thread:
Posted by CrAzYmEd on May 24, 2010, at 22:42:05
In reply to Re: Also » CrAzYmEd, posted by Phillipa on May 23, 2010, at 12:18:09
Not sure what your asking Phillipa but lisuride has a interesting pharmacological profile wich makes it interesting for ppl like us. While its being used for parkinson, it has potential for other things too.
Posted by Brainbeard on May 24, 2010, at 22:42:05
In reply to Re: Also, posted by CrAzYmEd on May 23, 2010, at 12:25:01
A potent 5HT1A-agonist could be a key ingredient in an antidepressant cocktail, as Dr. Stahl has marked out. An (S)SRI, a 5HT2A-antagonist and a 5HT1A-agonist, plus perhaps a D2-antagonist, make for a theoretically ideal antidepressant combo, according to Stahl.
Several potent 5HT1A-agonists never made it onto the market, since they weren't very effective as standalone drugs. I thought we were stuck with Buspar (buspirone). Lisuride could be worth its while when added to the right combo. As a standalone drug, I don't expect it to yield very impressive results. Would be glad to be proven wrong though. Will google this stuff to see if I can get it.
Posted by CrAzYmEd on May 24, 2010, at 22:42:05
In reply to Interesting - Could Be Key Ingredient Of AD Combo, posted by Brainbeard on May 23, 2010, at 15:43:30
"A potent 5HT1A-agonist could be a key ingredient in an antidepressant cocktail, as Dr. Stahl has marked out. An (S)SRI, a 5HT2A-antagonist and a 5HT1A-agonist, plus perhaps a D2-antagonist, make for a theoretically ideal antidepressant combo, according to Stahl."
I think that 5HT2A AGONISM is better then antagonism, while 5HT2A agonism has also negative effects, 5HT1A agonism seems to completely nullify it (lisuride is a antidepressant/anxiolytic despite its very potent 5HT2A agonism). I beleive that with 5HT1A agonism, 5HT2A AGONISM is the way to go as 5HT2A agonism would increase dopamine in the mesolimbic area's.
5HT2A is also of crucial importance of regulating dopamine release by amp/opiates
"5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants"Also D2 and D4 agonism are important, D2 is implicated in efford related decission making, so lisuride can be motivating.
Dopamine is also implicated in social anxiety, so D2 agonism would be of benefit it, and not D2 antagonism (wich i think is a bad idea overall, agonism is the way to go).But yeah i agree that this one would do very well in combo's, and imo also on its own.
Posted by CrAzYmEd on May 24, 2010, at 22:42:05
In reply to Re: Interesting - Could Be Key Ingredient Of AD Combo, posted by CrAzYmEd on May 23, 2010, at 16:06:54
Why i think lisuride would work on its own, is because it does alot more then just 5HT1A agonism.
Posted by Brainbeard on May 24, 2010, at 22:42:05
In reply to Re: Interesting - Could Be Key Ingredient Of AD Combo, posted by CrAzYmEd on May 23, 2010, at 16:06:54
5HT2A receptors INHIBIT dopamine, my good friend. So AGONIZING them may boost dopamine in certain area's of the brain only by inhibiting it in other area's.
Agonism may yield results similar to antagonism through downregulation and similar mechanisms. Remember that SSRI's are only effective after weeks to months because only then the therapeutical effects of indirect 5HT2A-agonism (through flooding the brain with serotonin=5HT) become manifest. Still, 5HT2A/C-antagonism appears to be a better way to boost dopamine than ditto agonism.
D2 agonism can promote psychotic symptoms and weird thought patterns.
D4 receptors are involved with prefrontal information processing. An experimental D4-ANTAGONIST has been shown to REDUCE stress induced cognitive debilitation.
The ' atypical typical' antipsychotic pipamperone is a potent D4-antagonist and this has been theorized to be one of the mechanisms behind its therapeutic potential for mood disorders.. together with 5HT2A-antagonism.There is evidence to suggest that D2-antagonism combined with serotonin reuptake inhibition boosts dopamine transmission in the prefrontal cortex: http://www.nature.com/npp/journal/v30/n1/abs/1300567a.html
> Dopamine is also implicated in social anxiety, so D2 agonism would be of benefit it, and not D2 antagonism (wich i think is a bad idea overall, agonism is the way to go).
Like most all of us, including my good self, you're oversimplifying way too much here. You're jumping from dopamine in general to D2 agonism. Risperdal is a drug that has helped many with social anxiety, often as an add-on to an SSRI. Risperdal is a 5HT2A-antagonist and a D2-antagonist.
Dopamine agonism is not what you may think it is: it fools the brain into thinking there is more dopamine around, without actually increasing dopaminergic transmission! That's why dopamine agonists can have such non-dopaminergic side-effects as causing one to fall asleep in the middle of activity (all synthetic D2-agonists can cause sleep attacks, with the noteable exception of piribedil=Trivastal)!
Posted by CrAzYmEd on May 24, 2010, at 22:42:06
In reply to Let's Have Dopamine Pie For Lunch, posted by Brainbeard on May 23, 2010, at 16:39:49
"5HT2A receptors INHIBIT dopamine, my good friend. So AGONIZING them may boost dopamine in certain area's of the brain only by inhibiting it in other area's."
--- If i'm correct 5HT2A antagonism boosts dopamine in the same area's as 5HT1A agonism, but 5HT2A agonism increases dopamine in mesolimbic area's, thus making the combo of 5HT1A/5HT2A agonism the most interesting.
"D2 agonism can promote psychotic symptoms and weird thought patterns.'
----- Sure, in psychotic ppl it will make everything worse, HOWEVER that doesnt mean they will cause psychotic symptons if those that arent psychotic (for example look at all the studies regarding pramipexole, its generally well tolerated and has been shown VERY effective for depression.
A good friend of me with social anxiety has been on pramipexole for months for he's social anxiety,with great succes, however he did get anhedonia, wich is caused by D3 agonism (D3 preferring agonists cause gambling by blunting reward).
"D4 receptors are involved with prefrontal information processing. An experimental D4-ANTAGONIST has been shown to REDUCE stress induced cognitive debilitation.
The ' atypical typical' antipsychotic pipamperone is a potent D4-antagonist and this has been theorized to be one of the mechanisms behind its therapeutic potential for mood disorders.. together with 5HT2A-antagonism."---- Agreed, however both agonism and antagonism can have differend positive effects for many receptors.
"There is evidence to suggest that D2-antagonism combined with serotonin reuptake inhibition boosts dopamine transmission in the prefrontal cortex: http://www.nature.com/npp/journal/v30/n1/abs/1300567a.html"
----Presynaptic antagonism.
"Dopamine agonism is not what you may think it is: it fools the brain into thinking there is more dopamine around, without actually increasing dopaminergic transmission! That's why dopamine agonists can have such non-dopaminergic side-effects as causing one to fall asleep in the middle of activity (all synthetic D2-agonists can cause sleep attacks, with the noteable exception of piribedil=Trivastal)!"
-----I know, however autoreceptors up/downregulate, so with chronic administration the side effects will greatly reduce leaving you with more D2 activation, i'm aware of the autoreceptors;).
"Like most all of us, including my good self, you're oversimplifying way too much here. You're jumping from dopamine in general to D2 agonism. Risperdal is a drug that has helped many with social anxiety, often as an add-on to an SSRI. Risperdal is a 5HT2A-antagonist and a D2-antagonist."
---- While i agree that it would help anxiety, i beleive that dopamine agonism in combination with 5HT1A agonism is the way to go. Dopamine agonism in some brainarea's causes anxiety, however 5HT1A agonism fully counteracts that (as lisuride doesnt cause any increase in anxiety but is highly anxiolytic), so the benefits of D2 agonism show up.
Dopamine boosting drugs are far better for SA then risperdal SSRI, for example amphetamine is considered the most effective med for it on the SA forum i post.
Or sulpiride AMI, a friend of me has great succes with that combo, the sulpiride blocks the presynaptic's, so the prami fully agonizes the postsynaptic receptors.
Posted by CrAzYmEd on May 24, 2010, at 22:42:06
In reply to Re: Let's Have Dopamine Pie For Lunch, posted by CrAzYmEd on May 23, 2010, at 17:03:03
Also would like to add that i dont find it justified to take antipsychotics for anxiety/depression with the risk of getting tardive dyskinesia. Let alone the link with diabetis.
Antipsychotics shouldnt be used for anything else then psychotic disorders.
Posted by Brainbeard on May 24, 2010, at 22:42:06
In reply to Re: Let's Have Dopamine Pie For Lunch, posted by CrAzYmEd on May 23, 2010, at 17:03:03
> Dopamine boosting drugs are far better for SA then risperdal SSRI, for example amphetamine is considered the most effective med for it on the SA forum i post.
Let's have it clear that dopamine agonists do NOT boost dopamine directly. You can hardly compare amphetamines with dopamine agonists.
>
> Or sulpiride AMI, a friend of me has great succes with that combo, the sulpiride blocks the presynaptic's, so the prami fully agonizes the postsynaptic receptors.Low dose sulpiride blocks dopamine autoreceptors, which regulate and inhibit dopamine release. Risperdal probably also blocks dopamine autoreceptors. Amisulpride does it for sure. Blocking DA autoreceptors increases dopaminergic transmission. Flupentixol also does it, although it hasn't conclusively been proven. Still, both sulpiride and amisulpride are antidopaminergics potent enough to cause hyperprolactinemia even in low doses (same goes for Risperdal).
You seem to be a little biased about lisuride. You've made your conclusions on what's ' the way to go', based on.. what? Preliminary evidence? Results in the brains of mice? I do this all the time, but it's in the real life that a drug has to prove what it's worth. Please eat this stuff and enlighten us.
Posted by CrAzYmEd on May 24, 2010, at 22:42:06
In reply to Lisuride And The Real Life, posted by Brainbeard on May 23, 2010, at 17:17:50
I know that dopamine agonists and amp are a differend animal, just gave an example.
"Low dose sulpiride blocks dopamine autoreceptors, which regulate and inhibit dopamine release. Risperdal probably also blocks dopamine autoreceptors. Amisulpride does it for sure. Blocking DA autoreceptors increases dopaminergic transmission. Flupentixol also does it, although it hasn't conclusively been proven. Still, both sulpiride and amisulpride are antidopaminergics potent enough to cause hyperprolactinemia even in low doses (same goes for Risperdal)."
--- Agreed.
"You seem to be a little biased about lisuride. You've made your conclusions on what's ' the way to go', based on.. what? Preliminary evidence? Results in the brains of mice? I do this all the time, but it's in the real life that a drug has to prove what it's worth. Please eat this stuff and enlighten us."
I'l give you an example of why i'm excited about this med:
Lets take a look at tandospirone (a potent 5HT1A agonist)"Tandospirone is typically used at a dose of 30 mg/daily[6] taken in divided doses of 10 mg three times per day due to its short half-life. Though originally considered a relatively weak anxiolytic agent,[6] a clinical study found that doubling the dose to 60 mg/daily resulted in a "remarkable anxiolytic effect with an early onset of action, and without significant adverse effects", as well as "excellent anxiolytic efficacy that is comparable to that of the benzodiazepines".[6] [7]"
Lisuride has this property too its dopamine agonism (with alpha 2 antagonism) kinda like tandospirone and trivastal in one so to speak, and besides that we have 5HT7 antagonism wich also is usefull in depression. (5HT7 antagonism potentias antidepressants in mice, and blocking the 5HT7 antaogonism abolishes the antidepressant effect of amisulpiride)
Also note the magic word "potential" i'm not saying lisuride is the magic bullit, just that it has alot of potential.
Posted by CrAzYmEd on May 24, 2010, at 22:42:06
In reply to Re: Also, posted by CrAzYmEd on May 23, 2010, at 12:25:01
But you are right there is no way to know "the way to go" it really depends on the situation, for example look at this study. 5HT2A agonists may be of benefit for OCD patients.
"
17) Perani D, Garibotto V, Gorini A, Moresco RM, Henin M, Panzacchi A, Matarrese M, Carpinelli A, Bellodi L, Fazio F
In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naive obsessive-compulsive disorder.
Neuroimage. 2008 Apr 27;
There are several lines of evidence, the majority indirect, suggesting that changes in serotonergic or dopaminergic neurotransmission may contribute to the pathogenesis of obsessive-compulsive disorder (OCD). We evaluated the co-occurrence of serotonergic and dopaminergic dysfunctions in OCD subjects, all drug-naive, with no co-morbidity and homogeneous for symptoms. Each subject underwent two positron emission tomography (PET) scans to measure in vivo both serotonin (5-HT(2A)) and dopamine (D(2)) receptor distribution. For this, we used [(11)C]MDL and [(11)C]Raclopride, highly selective antagonists of 5-HT(2A) and D(2) receptors, respectively. The comparison with a control group was carried out using both voxel-wise (SPM2) and regions of interest (ROI) approaches. There was a significant reduction of 5-HT(2A) receptor availability in frontal polar, dorsolateral, and medial frontal cortex, as well as in parietal and temporal associative cortex of OCD patients. We also found a significant correlation between 5-HT(2A) receptor availability in orbitofrontal and dorsolateral frontal cortex and clinical severity, suggesting a specific role for serotonin in determining the OCD symptoms. There was also a significant reduction of [(11)C]Raclopride uptake in the whole striatum, particularly in the ventral portion, possibly reflecting endogenous dopaminergic hyperactivity. The co-existence of serotonergic and dopaminergic dysfunction in the same homogeneous group of drug-naive OCD patients provides in vivo evidence for the complex molecular mechanisms of OCD, and represents the basis for further studies on the effect of therapeutic agents with specific modulatory effects on these neurotransmission systems. [PubMed Citation] [Order full text from Infotrieve]"
My point is that 5HT2A antagonism seems to be considered as allways good on these forums, and D2 antagonism should be the way to go too, while i disagree with both, it depends on the situation, and i beleive that many cases the other way around is good, those options seem to be ignored, 5HT2A is allways deemed as "bad".
Posted by linkadge on May 24, 2010, at 22:42:07
In reply to Re: Let's Have Dopamine Pie For Lunch, posted by CrAzYmEd on May 23, 2010, at 17:03:03
Pretty much all dopamine agonists have a U shaped theraputic window for their theraputic effects.
Dopamine in the prefrontal cortex can enhance cognition, but (in the stress model that Brainbeard mentioned) a anxiogenic beta carboline was used which can greatly enhance dopamine neurotransmission. If it gets too high, there is cognative disturbance.
The same thing goes with dopamine in the NAC. If dopamine levels get too high, they can produce apathy and anhedonia just as if levels are too low.
I would say that the 5-ht2c antagonism has a greater effect on dopamine in the neucleus accumbens. The 5-ht2 receptors affect the prefrontal cortex more.
Linkadge
Posted by linkadge on May 24, 2010, at 22:42:07
In reply to Re: Let's Have Dopamine Pie For Lunch, posted by CrAzYmEd on May 23, 2010, at 17:06:40
I would use a low dose of a typical AP such as perphenazine if dopamine antagonism is desired. There is low risk of TD as well as diabets.
Linkadge
Posted by linkadge on May 24, 2010, at 22:42:07
In reply to Re: Also, posted by CrAzYmEd on May 23, 2010, at 17:42:05
Is this med a 5-ht2b agonist? LSD is. This is very bad for cardiac valves. This is why cabergoline was pulled.
Linkadge
Posted by Brainbeard on May 24, 2010, at 22:42:08
In reply to Lisuride And The Real Life, posted by Brainbeard on May 23, 2010, at 17:17:50
I found a lisuride experience of somebody who took it to induce hypersexuality here: http://www.asiatour.com/lisuride1.htm. It starts off with some interesting description of initial lisuride use, then wanders off into irrelevant musings. Don't bother with the second part, it hardly addresses lisuride at all anymore.
I also found a research abstract which illustrates my point that dopamine agonists are not dopamine boosters. It (http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TBR-44PC749-13&_user=10&_coverDate=02/28/2002&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1345452728&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=1adc7e92e2efacbb18286e0a1442e749) says: ' This study supports the view that alcoholics may relapse due to decreased dopamine function, resulting from intake of dopamine D2 receptor agonists. In particular, our data do not support the use of lisuride for relapse prevention in alcoholics.'
There you have it. Lisuride and other D2-agonists may decrease dopamine function, at least in part.
On the other hand, lisuride yields EEG's similar to psychostimulants: http://www.erowid.org/references/refs_view.php?ID=3243
From a patent to use liusuride in alcoholism (http://www.freepatentsonline.com/4096266.html):
'Lisuride (.....) was synthesized by Zikan and Semonsky (Zikan, V., M. Semonsky: Coll. Czech. Chem. Commun. (1960), 1922) in order to develop an LSD-25 analog with antiserotonin and antihistamine properties without having hallucinogenic side effects. (.....)
In one of the first clinical trials, Vojtechovsky et al (Activ. Nerv. Super. 5 (1963), 211) found in about half of the cases a moderate inhibitive dysphoric effect, while in about one third they found a slight central nervous system (CNS) effect without autonomous symptoms. In half of the subjects, however, the changes were so slight that they could not be distinguished from placebo. Lisuride did not alter the mental functions in psychological tests. (.....)'
The article also points out that lisuride can be effective against migraines as well as neurasthenia.
Incredible potential? A 'moderate inhibitive dysphoric effect' or a 'slight central nervous system effect' doesn't sound all that fancy to me. As a standalone drug, I think lisuride has only limited use.
Posted by CrAzYmEd on May 24, 2010, at 22:42:08
In reply to Re: What about 5-ht2b? Bad for cardiac valves?, posted by linkadge on May 23, 2010, at 18:06:15
Linkadge, its a 5HT2B antagonist, it wont cause cardiovascular damage.
Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis.
Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, Latté KP, Palla D, Schurad B.Global Medical Safety, Schering AG, Berlin, Germany. [email]christoph.hofmann@schering.de[/email]
Abstract
OBJECTIVES: The high incidence of fibrotic cardiac valvulopathies reported in association with the 8beta-ergoline dopamine (DA) agonist, pergolide, and also case reports for cabergoline and bromocriptine have made it necessary to review the theoretical basis and actual findings in the case of another DA agonist, the 8alpha-ergoline lisuride (used since the 1970s for migraine prophylaxis as well as since the 1980s for its prolactin-lowering and anti-Parkinson activity). METHODS: We have reviewed the pharmacology of lisuride in relation to other DA agonists, and we have performed a throughout literature search as well as a search of our own and other adverse drug reaction databases for a possible relationship of lisuride with cardiac valvulopathy or for any reports of fibrosis in other locations. RESULTS: Our review of the pharmacology and the literature strongly suggests that drug-induced cardiac valvulopathies are always related to a stimulatory drug effect on trophic 5-HT(2B) receptors. As lisuride is devoid of such an effect, but on the contrary is an extremely potent 5-HT(2B) antagonist, an association of lisuride therapy with cardiac valvulopathies seems to be highly unlikely. In agreement with this hypothesis, not a single report of a cardiac valvulopathy associated with lisuride therapy has been identified in any database so far.Furthermore, against a background of an estimated 360,000 patient years, we have found only a very small number of cases of any other form of fibrosis (1x retroperitoneal, 2x pleural, 2x pulmonary, 1x interstitial pulmonary changes), in part combined with other risk factors and confounding variables. This closely matches 4 reports available from WHO (1x retroperitoneal, 3x pleural fibrosis). In addition, only 5 other possibly related conditions (3x pleural effusion, 1x pleuritis, 1x pericarditis) were identified in the lisuride adverse drug reaction database of Schering, Berlin. CONCLUSIONS: No link has been found between lisuride use and fibrotic cardiac valvulopathy, in agreement with the 5-HT(2B) receptor antagonist effect of this drug. The very low incidence of spontaneous reports of any other fibrosis could be even compatible with an association by chance in the population exposed to lisuride. Although close monitoring for this kind of side effects is still to be recommended in the therapy with lisuride, our data do not support the concept of a class effect suggesting that all ergot-derived drugs and especially DA receptor agonists with some chemical similarity to the ergot structure will cause or facilitate cardiac valvulopathies as observed with pergolide.
Posted by CrAzYmEd on May 24, 2010, at 22:42:08
In reply to Lisuride Experiences: Mixed Bag, Not The New Cool, posted by Brainbeard on May 23, 2010, at 18:13:42
brainbeard: Those studies where they described a moderate effect, was lisuride used for several weeks or acutely? Negative effects can be expected the first weeks due to a decrease in dopaminergic transmission.
(Yeah i know dopamine agonists decrease dopamine at first, but this completely recovers after a while, leaving you with the originial dopamine transmission the dopamine agonism."After 14 days of PPX treatment, the firing rate of DA had recovered as well as that of NE, whereas the firing rate of 5-HT neurons was increased by 38%. It was also observed that sustained PPX administration produced desensitization of D(2)/D(3) and 5-HT(1A) cell body autoreceptors, as well as a decrease in sensitivity of alpha(2)-adrenergic cell body autoreceptors. These adaptive changes are implicated in long-term firing rate adaptations of DA, NE and 5-HT neurons after prolonged PPX administration. In conclusion, the therapeutic action of PPX in depression might be attributed to increased DA and 5-HT neurotransmission."
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).'
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