![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 10 to 34 of 98. Go back in thread:
Posted by CrAzYmEd on May 24, 2010, at 22:41:59
In reply to Re: to crazymed, posted by CrAzYmEd on May 23, 2010, at 10:03:38
As its a dopamine agonist, the same adaptation period as with other dopamine agonists can be expected, so it would take a few weeks to start fully working. It should also be slowly titrated up or the adaptation wont be fun.
Posted by SLS on May 24, 2010, at 22:41:59
In reply to Re: to crazymed, posted by CrAzYmEd on May 23, 2010, at 10:03:38
I'm glad lisuride isn't cardiotoxic. I became concerned after reading what you posted about 5-HT1b receptors.
- Scott-------------------------------------------------
> Pharmacological profile
>
> Lisuride is a:
> 5HT1A agonist
> 5HT1B agonist
> 5HT2A agonist
> 5HT2C agonist
> 5HT6 agonist
> 5HT7 antagonist
> 5HT5A didnt find yet
> D2 agonist
> D4 agonist
>
> According to the journal not significant:
> 5ht1e
> D5
> H2
> D3
> And interacts with several andronergic receptors.
>
> It has a short half life tough, like ritalin thats a bit of a downside.
Posted by SLS on May 24, 2010, at 22:41:59
In reply to Also, posted by CrAzYmEd on May 23, 2010, at 10:10:38
> As its a dopamine agonist, the same adaptation period as with other dopamine agonists can be expected, so it would take a few weeks to start fully working. It should also be slowly titrated up or the adaptation wont be fun.
My impression of DA (D2, D3) agonists is that they don't make very good antidepressants, precisely because of the brain adaptations that occur while taking them. People seem to feel better almost immediately. However, diminishing returns are then seen with continued treatment. Again, this is just a personal observation.
- Scott
Posted by CrAzYmEd on May 24, 2010, at 22:42:00
In reply to Re: Also, posted by SLS on May 23, 2010, at 10:46:04
I think that memantine will be as use for that, as NMDA antagonists have been shown to upregulate D2/D3 and 5HT1A, and indeed NMDA antagonists have been found effective for tolerance to a wide variaty of drugs.
Posted by SLS on May 24, 2010, at 22:42:00
In reply to Re: Also, posted by SLS on May 23, 2010, at 10:46:04
> > As its a dopamine agonist, the same adaptation period as with other dopamine agonists can be expected, so it would take a few weeks to start fully working. It should also be slowly titrated up or the adaptation wont be fun.
> My impression of DA (D2, D3) agonists is that they don't make very good antidepressants, precisely because of the brain adaptations that occur while taking them. People seem to feel better almost immediately. However, diminishing returns are then seen with continued treatment. Again, this is just a personal observation.Of course, I would be extremely happy to hear from people personal experiences that contradict my impressions.
- Scott
Posted by SLS on May 24, 2010, at 22:42:00
In reply to Re: Also, posted by CrAzYmEd on May 23, 2010, at 10:49:57
> I think that memantine will be as use for that, as NMDA antagonists have been shown to upregulate D2/D3 and 5HT1A, and indeed NMDA antagonists have been found effective for tolerance to a wide variaty of drugs.
I have heard that legend told many times.
- Scott
Posted by CrAzYmEd on May 24, 2010, at 22:42:00
In reply to Re: Also, posted by SLS on May 23, 2010, at 10:51:04
Yeah some experiences regarding this med would be nice, maybe i am too excited, but this one really looks like it could have potential, and since it doesnt cause bad side effects like cardiovascular damage, id say it would be worth a try:)
Posted by SLS on May 24, 2010, at 22:42:02
In reply to Re: Also, posted by SLS on May 23, 2010, at 10:52:33
> > I think that memantine will be as use for that, as NMDA antagonists have been shown to upregulate D2/D3 and 5HT1A, and indeed NMDA antagonists have been found effective for tolerance to a wide variaty of drugs.
> I have heard that legend told many times.
The only evidence that seems convincing is that memantine can prevent tolerance to the nociceptive properties of opioids.
- Scott
Posted by SLS on May 24, 2010, at 22:42:03
In reply to Re: Also, posted by CrAzYmEd on May 23, 2010, at 10:53:46
> Yeah some experiences regarding this med would be nice, maybe i am too excited, but this one really looks like it could have potential, and since it doesnt cause bad side effects like cardiovascular damage, id say it would be worth a try:)
I eagerly look forward to watching how people react to lisuride. It is a very interesting drug. I'm glad you posted the information about it.
- Scott
Posted by CrAzYmEd on May 24, 2010, at 22:42:03
In reply to Re: Also, posted by SLS on May 23, 2010, at 10:54:59
Well, your about to learn more about their potential!
And those are the studies looking at D2/D3 and 5HT1A density:
Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat
G Micheletti, B Lannes, C Haby, E Borrelli, E Kempf, JM Warter, J Zwiller
Post to:
Twitter Facebook Linked-inDopamine D2 receptor gene expression was examined in rat striatum after chronic treatment with N-methyl-D-aspartate (NMDA) receptor antagonists (ketamine at 15 mg/kg/day or MK-801 at 0.1, 0.2 and 0.4 mg/kg/day per os, for 50 days). The long-isoform mRNA, as well as the total D2 mRNA expression were induced. No change was noticed in striatal dopamine release or turnover. D2 binding studies carried out in MK-801 chronically treated (0.3 mg/kg/day per os, for 50 days) and control rats revealed an increased receptor density in treated animals without a significant change in receptor affinity. These results suggest that the synthesis of both striatal D2 receptor isoforms is postsynaptically regulated at the transcriptional level, by events triggered by glutamate through the NMDA-type receptor.
Quote:
Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior.
Author: Mele, A : Cabib, S : Oliverio, A
Citation: Psychopharmacology-(Berl). 1995 Feb; 117(3): 313-7
Abstract: The effects of pretreatment with the non-competitive NMDA antagonist ( )MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day x 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors.
Quote:
Summary. Behavioral changes have previously been reported following administrations of uncompetitive NMDA receptor antagonists memantine, amantadine and MK-801 for 14 days, at the doses that produce plasma levels comparable to those seen in patients (20, 100 and 0.31 mg/kg/day respectively). Using the same doses, the effect on receptor binding (autoradiography) was studied in rats. [3H]MK-801 binding was increased in the dentate gyrus and CA3 region of the hippocampus (35.2 and 24.3% respectively) following 3 days S.C. infusion of memantine by ALZET minipumps. One daily injection of memantine for 14 days, increased [3H]MK-801 binding in the frontal cortex by 40.3%. The same treatment with amantadine did increase [3H]raclopride binding to dopamine D2 receptors by 13.5%. None of these treatments changed the expression of muscarinic receptors. It is concluded that subchronic blockade of the NMDA receptor by uncompetitive antagonists at moderate (therapeutically-relevant) doses induced only minor changes in NMDA and dopamine D2 receptor expression.
Quote:
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-naďve, 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.
Quote:
Effect of combined treatment with imipramine and amantadine on the central dopamine D2 and D3 receptors in rats.
Rogóz Z, Dlaboga D, Dziedzicka-Wasylewska M.Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. rogoz@if-pan.krakow.pl
In spite of intensive research, the problem of treating antidepressant-resistant depressive patients has not yet been solved. Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptors, amantadine (AMA), produced stronger "antidepressant" effect in the forced swimming test (Porsolt's test) than the treatment with either drug alone given. Since it has been suggested that dopamine receptors, among others, may play a role in anti-immobility effect of IMI, in the present study we examined the effect of AMA (10 mg/kg) and IMI (5 and 10 mg/kg) given separately or jointly, as a single dose or repeatedly (twice daily for 14 days) on the dopamine D2 and D3 receptors in the rat brain, using receptor autoradiography. Following repeated administration of AMA alone or given in combination with IMI (5 mg/kg), the binding of [3H]quinpirole (dopamine D2/D3 receptors agonist) was increased, and similar changes were observed at the level of mRNA encoding dopamine D2 receptors. We used [3H]7-OH-DPAT to selectively label the dopamine D3 receptors. This experiment has shown that AMA given repeatedly did not induce statistically significant changes in the D3 receptor binding, while IMI at both used doses, increased the [3H]7-OH-DPAT binding, and this effect was still observed after repeated joint administration of AMA with both doses of IMI. However, using both radioligands, we did not observe any synergistic or even additive effects in the binding studies after joint administration of AMA and IMI. Nevertheless, we can conclude that repeated administration of AMA, given together with IMI, induces the up-regulation of dopamine D2 and D3 receptors in the rat brain, and this effect may explain their synergistic action observed in the behavioral studies involving dopaminergic transmission.Modulation of dopamine D2 receptor expression by an NMDA receptor antagonist in rat brain.
Nair VD, Savelli JE, Mishra RK.Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada.
The expression of dopamine D2 receptor mRNA was studied in rat brain following micro-injection of a competitive N-methyl D-aspartate (NMDA) receptor antagonist at the prefrontal cortex. Male Sprague-Dawley rats cannulated bilaterally into the medial prefrontal cortex were injected with a competitive NMDA receptor antagonist ( /-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). The levels of mRNA for NMDA-R1 and dopamine D2 receptors were measured by reverse transcriptase-polymerase chain reaction (RT-PCR), and D2 receptor density was quantified by [3H]spiperone binding in the cortex and striatum of these animals. In the prefrontal cortex, the levels of NMDA-R1 receptor mRNA showed significant decrease in CPP-treated animals compared to control animals. However, NMDA-R1 mRNA levels in striatum remained unchanged in any of the experimental groups. The D2 receptor mRNA levels and [3H]spiroperidol binding in prefrontal cortical membranes showed no significant difference between the CPP-treated and control groups of animals. In the striatum, a significant increase in striatal dopamine D2 receptor mRNA levels was shown in animals treated with CPP. The increase in D2 mRNA level was correlated with an increase in the D2 receptor binding sites in the striatal membranes. These results suggest a possible interaction between prefrontal cortical NMDA receptors and striatal dopamine receptors.
Quote:
J Mol Neurosci. 1998 Oct;11(2):121-6.
Modulation of dopamine D2 receptor expression by an NMDA receptor antagonist in rat brain.
Nair VD, Savelli JE, Mishra RK.Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada.
The expression of dopamine D2 receptor mRNA was studied in rat brain following micro-injection of a competitive N-methyl D-aspartate (NMDA) receptor antagonist at the prefrontal cortex. Male Sprague-Dawley rats cannulated bilaterally into the medial prefrontal cortex were injected with a competitive NMDA receptor antagonist ( /-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). The levels of mRNA for NMDA-R1 and dopamine D2 receptors were measured by reverse transcriptase-polymerase chain reaction (RT-PCR), and D2 receptor density was quantified by [3H]spiperone binding in the cortex and striatum of these animals. In the prefrontal cortex, the levels of NMDA-R1 receptor mRNA showed significant decrease in CPP-treated animals compared to control animals. However, NMDA-R1 mRNA levels in striatum remained unchanged in any of the experimental groups. The D2 receptor mRNA levels and [3H]spiroperidol binding in prefrontal cortical membranes showed no significant difference between the CPP-treated and control groups of animals. In the striatum, a significant increase in striatal dopamine D2 receptor mRNA levels was shown in animals treated with CPP. The increase in D2 mRNA level was correlated with an increase in the D2 receptor binding sites in the striatal membranes. These results suggest a possible interaction between prefrontal cortical NMDA receptors and striatal dopamine receptors.
And about 5HT1A:
Quote:
Single doses of MK-801, a non-competitive antagonist of NMDA receptors, increase the number of 5-HT1A serotonin receptors in the rat brainK. Wdzony*, M. Ma
kowiak, A. Czyrak, K. Fijał and B. Michalska
Institute of Pharmacology, Polish Academy of Sciences, 12 Smtna Street, PL-31-343 Kraków, Poland
Accepted 22 January 1997. Available online 22 July 1997.
Abstract
In the present study, we investigated the impact of MK-801, a non-competitive NMDA receptor antagonist, on the density of serotonergic receptors of the 5-HT1A subtype and on the metabolism of serotonin in various regions of the rat brain containing terminals and cell bodies of serotonergic neurons. The binding of [3H]8-OH-DPAT to 5-HT1A serotonin receptors was increased after MK-801 (0.4 mg/kg) as was shown by autoradiographic studies in the frontal, cingulate and part of enthorinal cortex, subregions of the hippocampus and raphe nuclei. The above receptor changes were observed at 2 h and, in some brain regions, at 24 h after MK-801. In saturation binding studies, an increase in the Bmax value in the rat hippocampus was found after MK-801 (0.4 mg/kg) while no changes being noted in the Kd value. MK-801 (0.4 mg/kg) increased the concentration of the serotonin metabolite 5-HIAA in the prefrontal cortex and hippocampus, respectively, at 2 and 3 or 3 h after administration, being without effect on the level of serotonin. In the dorsal raphe nucleus, MK-801 (0.4 mg/kg) decreased the level of serotonin without affecting the level 5-HIAA (0.5 h after administration) or increased the level of 5-HIAA without altering the concentration of serotonin (3 h after administration). It is concluded that single administration of MK-801 may alter the density of serotonergic 5-HT1A receptors and in consequence influence the function of the central nervous system associated with activation of 5-HT1A receptors.
Posted by CrAzYmEd on May 24, 2010, at 22:42:04
In reply to Re: Also, posted by CrAzYmEd on May 23, 2010, at 10:59:27
My first link to the SAS forum contains evidence that nmda antagonists prevent tolerance to variaty of drugs a collection of all anecdotal reports i found regarding it.
Posted by SLS on May 24, 2010, at 22:42:04
In reply to Re: Also, posted by CrAzYmEd on May 23, 2010, at 11:00:56
> My first link to the SAS forum contains evidence that nmda antagonists prevent tolerance to variaty of drugs a collection of all anecdotal reports i found regarding it.
Thanks for all of the information! I'll have to read it later.
Can memantine reverse tolerance after it occurs?
- Scott
Posted by CrAzYmEd on May 24, 2010, at 22:42:04
In reply to Re: Also » CrAzYmEd, posted by SLS on May 23, 2010, at 11:12:07
Il give an example
User is tolerant to amphetamine, when adding memantine he will stay tolerance, however when stopping the amp the tolerance will go down faster then without memantine, and when starting amp again tolerance will go up much slower. (this is based on all the anecdotal reports.
How this will work out with lisuride i dont know, its most interesting action is the potent 5HT1A agonism, wich may not even build a rapid tolerance at all. So maybe lisuride wont even build that much tolerance. There are no reports so we dont really know.
Posted by Phillipa on May 24, 2010, at 22:42:04
In reply to Re: Also, posted by CrAzYmEd on May 23, 2010, at 11:17:50
When I googled it it said parkinson's, migraines, and sex I don't get why if a disease like parkinson's needs dopamine why do those with depression? Phillipa
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
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