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OD Moderators: Keif’ Richards | negrogesic
L-DOPA
- Thread starter quale
- Start date
zorn
Bluelighter
I wouldn't be so quick to judge that.... an online search yielded a couple web sites claiming levodopa had some abuse potential. Apparently it can also sometimes precipitate a schizophrenia-like psychosis, a sign it has some effect. Cmon, no BLer's have tried this?
Incidentally you want to get it combined with carbidopa, a peripheral decarboxylase inhibitor that doesn't cross the BBB, which prevents it from being transformed into dopamine outside the brain. I wanna try this with 5-HTP, too.
Incidentally you want to get it combined with carbidopa, a peripheral decarboxylase inhibitor that doesn't cross the BBB, which prevents it from being transformed into dopamine outside the brain. I wanna try this with 5-HTP, too.
FordPrefect
Bluelighter
- Joined
- Oct 24, 2001
- Messages
- 201
http://cbshealthwatch.medscape.com/cx/viewarticle/402928
Psychiatric Side Effects.
The major adverse effects of the drug are psychiatric. Patients taking levodopa, especially in combination with other drugs, can experience the following:
* Confusion.
* Extreme emotional states, particularly anxiety.
* Vivid dreams.
* Visual and possibly auditory hallucinations.
* The drug may even unmask dementia that had not been previously noticed.
Psychiatric Side Effects.
The major adverse effects of the drug are psychiatric. Patients taking levodopa, especially in combination with other drugs, can experience the following:
* Confusion.
* Extreme emotional states, particularly anxiety.
* Vivid dreams.
* Visual and possibly auditory hallucinations.
* The drug may even unmask dementia that had not been previously noticed.
its420time
Bluelighter
A good movie with L-DOPA in it is The Awakening.
PhreeX
Bluelight Crew
No, you can't abuse it, it's effects are to subtle..
AbraMontague
Bluelighter
- Joined
- Dec 31, 2000
- Messages
- 1,006
There is no euphoria from it but if you take it over a long period of time (like if you have Parkinson's), you might start to develop chemical psychosis symptoms from all the dopamine in your brain.
From Nueropsychopharmacology I am told
Cocaine blocks the uptake of DA, 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in the CNS. However, the determination of which of these actions is associated with its reinforcing effects has only recently been elucidated. There is a significant positive correlation between the potencies of cocaine and some related compounds as DA uptake blockers and their ability to serve as reinforcers in self-administration studies in the rhesus monkey (76 ). In contrast, significant correlations between the reinforcing effects and blockade of uptake of NE and 5-HT have not been found. These data strongly suggest that it is the blockade of the uptake of DA that is an essential step in the mediation of the reinforcing effects of cocaine.
If the Dopamine reuptake inhibition is relevant to reinforcement I would strongly suspect it is relevant to making you feel good. The same source tells me amphetamine reverses the DA reuptake pump (among its many effects) so I am curious what leads you to believe the dopagenic effects aren't the important ones.
Cocaine blocks the uptake of DA, 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in the CNS. However, the determination of which of these actions is associated with its reinforcing effects has only recently been elucidated. There is a significant positive correlation between the potencies of cocaine and some related compounds as DA uptake blockers and their ability to serve as reinforcers in self-administration studies in the rhesus monkey (76 ). In contrast, significant correlations between the reinforcing effects and blockade of uptake of NE and 5-HT have not been found. These data strongly suggest that it is the blockade of the uptake of DA that is an essential step in the mediation of the reinforcing effects of cocaine.
If the Dopamine reuptake inhibition is relevant to reinforcement I would strongly suspect it is relevant to making you feel good. The same source tells me amphetamine reverses the DA reuptake pump (among its many effects) so I am curious what leads you to believe the dopagenic effects aren't the important ones.
Exactly. How would blocking the reuptake of dopamine be aided by more dopamine available in your axons? It doesn't mean dopamine is going to be more released into your synapse and thus be aided by cocaine. As for methamphetamine, how effective is it at releasing dopamine? I was always under the impression that its effects on the dopamine system were minimal compared to other systems. But if you can show me evidence that differs I'd love to see it so I know for sure.
zorn
Bluelighter
Aw, I just love it when someone references "The Fourth Generation of Progress." Great title. Good online book too.
Deus, meth's major effects are on the dopamine systems. The link quale gave has this somewhere. Meth blocks DA reuptake and at high doses directly precipitates its efflux from presynaptic neurons. It also has effects on NE and SE, but the dopaminergic effects are believed to be central to its effects. It is also neurotoxic at DA terminals much the same way MDMA is at 5-HT terminals. Incidentally all addictive/abused drugs, except psychedelics, directly or indirectly cause dopamine release, the level of which (in the nucleus accumbens) is nearly perfectly correlated with objective measures of their "addictiveness." Rats will do nearly anything for a injection of dopamine directly into the nucleus accumbens... I am guessing any one of us would too, if only we knew.
It's also unclear a priori how the body's homeostatic regulatory mechanisms would respond to an excess of l-dopa. I can come up with a few BS models where there more l-DOPA -> more DA efflux. Since it causes psychotic symptoms, that suggests to me that the additional synthesized dopamine is getting released somewhere.
quale, you fake Parkinson's and snag a script for some sweet l-DOPA, and I'll bang that shit.
-Zorn
Deus, meth's major effects are on the dopamine systems. The link quale gave has this somewhere. Meth blocks DA reuptake and at high doses directly precipitates its efflux from presynaptic neurons. It also has effects on NE and SE, but the dopaminergic effects are believed to be central to its effects. It is also neurotoxic at DA terminals much the same way MDMA is at 5-HT terminals. Incidentally all addictive/abused drugs, except psychedelics, directly or indirectly cause dopamine release, the level of which (in the nucleus accumbens) is nearly perfectly correlated with objective measures of their "addictiveness." Rats will do nearly anything for a injection of dopamine directly into the nucleus accumbens... I am guessing any one of us would too, if only we knew.
It's also unclear a priori how the body's homeostatic regulatory mechanisms would respond to an excess of l-dopa. I can come up with a few BS models where there more l-DOPA -> more DA efflux. Since it causes psychotic symptoms, that suggests to me that the additional synthesized dopamine is getting released somewhere.
quale, you fake Parkinson's and snag a script for some sweet l-DOPA, and I'll bang that shit.
-Zorn
"Ok, so now the two of you are saying not only does meth block the reuptake of dopamine but it also releases it? How is this possible?"
Heh, I thought you knew better than that Deus, like the poster above said, think MDMA.
Anyways, I think much of the meth euphoric effect actually comes from its effects on norepinephrine, I don't remember where I read that though....
Heh, I thought you knew better than that Deus, like the poster above said, think MDMA.
Anyways, I think much of the meth euphoric effect actually comes from its effects on norepinephrine, I don't remember where I read that though....
Xylo:
One of them said that meth causes the dopamine receptors to work in reverse. Dumping dopamine into the synapse.
The other one says that it blocks reuptake of dopamine.
If it blocks the reuptake of the dopamine it wouldn't beable to bind to the terminal and cause it to work in reverse.
I'm sorry am I missing something??
One of them said that meth causes the dopamine receptors to work in reverse. Dumping dopamine into the synapse.
The other one says that it blocks reuptake of dopamine.
If it blocks the reuptake of the dopamine it wouldn't beable to bind to the terminal and cause it to work in reverse.
I'm sorry am I missing something??
zorn
Bluelighter
Hmmm, perhaps it wouldn't be a bad idea to put together a "neurochemistry of drugs of abuse for beginners" FAQ.... mods?
Anyways, quale is correct. For good reviews of stimulant action, see [1] or [2]. [3] and [4] are research articles with more detail about the molecular action of amphetamine. Basically, amphetamine enters DA neurons by diffusing through the membrane or via the DA uptake transporter (DAT). It then acts at storage vesicles releasing DA into the cytoplasm, and also acts at the membrane to reverse the DAT. Incidentally, a large amount of DA in the cytoplasm will cause the DAT to reverse of its own accord, but amphetamine doesn't cause a sufficient intraceullular concentration to do this. Methamphetamine almost certainly functions similarly to amphetamine [no ref yet
].
xylo, you probably saw this in relation to the recent Synapse article [5]. This contains a long discussion about neurotransmitters being high, and has lots of good refs. There is indeed compelling evidence that dopamine is not the sole mediator of euphoria and stimulation; eg dopamine antagonists do not fully block the subjective effects of coke/amphetamine. It appears that DA is necessary but not sufficient for the stimulant high[5]. The authors propose that NE mediates the high and propose some experiments; I am certain we will see more research around this hypothesis in the upcoming years.
We should remember though that the brain is incredibly complex, and trying to associate different feelings with transmitters used in hundreds of millions of cells is probably a brutal oversimplification. As Rothmen et al put it, "Although it is tempting to speculate that stimulant induced positive subjective effects in humans are mediated by a single neurotransmitter, the more likely scenario is that multiple neurochemicals and brain regions contribute to the subjective experience described as the 'high'.... The possibility that NE contributes stimulant-induced positive subjective effects in humans does not rule out a role for DA in either subjective effects or stimulant addiction. For example, it is possible that even if a 'high' is mediated mostly by NE, the intense repetitive drug-taking behavior seen in severely addicted individuals is mediated by mesolimbic DA."
[1] Wise RA. Addictive drugs and brain stimulation reward. Annu Rev Neurosci 1996;19:319-40
[2] Seiden LS, Sabol KE, Ricaurte GA. Amphetamine: effects on catecholamine systems and behavior. Annu Rev Pharmacol Toxicol 1993;32:639-677.
[3] Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A. Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. Journal of Neuroscience, Vol 15, 4102-4108.
[4] Sara R. Jones, Raul R. Gainetdinov, R. Mark Wightman, and Marc G. Caron. Mechanisms of Amphetamine Action Revealed in Mice Lacking the Dopamine Transporter. Journal of Neuroscience, March 15, 1998, 18(6):1979-1986.
[5] Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 2001 Jan;39(1):32-41.
Anyways, quale is correct. For good reviews of stimulant action, see [1] or [2]. [3] and [4] are research articles with more detail about the molecular action of amphetamine. Basically, amphetamine enters DA neurons by diffusing through the membrane or via the DA uptake transporter (DAT). It then acts at storage vesicles releasing DA into the cytoplasm, and also acts at the membrane to reverse the DAT. Incidentally, a large amount of DA in the cytoplasm will cause the DAT to reverse of its own accord, but amphetamine doesn't cause a sufficient intraceullular concentration to do this. Methamphetamine almost certainly functions similarly to amphetamine [no ref yet
].xylo, you probably saw this in relation to the recent Synapse article [5]. This contains a long discussion about neurotransmitters being high, and has lots of good refs. There is indeed compelling evidence that dopamine is not the sole mediator of euphoria and stimulation; eg dopamine antagonists do not fully block the subjective effects of coke/amphetamine. It appears that DA is necessary but not sufficient for the stimulant high[5]. The authors propose that NE mediates the high and propose some experiments; I am certain we will see more research around this hypothesis in the upcoming years.
We should remember though that the brain is incredibly complex, and trying to associate different feelings with transmitters used in hundreds of millions of cells is probably a brutal oversimplification. As Rothmen et al put it, "Although it is tempting to speculate that stimulant induced positive subjective effects in humans are mediated by a single neurotransmitter, the more likely scenario is that multiple neurochemicals and brain regions contribute to the subjective experience described as the 'high'.... The possibility that NE contributes stimulant-induced positive subjective effects in humans does not rule out a role for DA in either subjective effects or stimulant addiction. For example, it is possible that even if a 'high' is mediated mostly by NE, the intense repetitive drug-taking behavior seen in severely addicted individuals is mediated by mesolimbic DA."
[1] Wise RA. Addictive drugs and brain stimulation reward. Annu Rev Neurosci 1996;19:319-40
[2] Seiden LS, Sabol KE, Ricaurte GA. Amphetamine: effects on catecholamine systems and behavior. Annu Rev Pharmacol Toxicol 1993;32:639-677.
[3] Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A. Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. Journal of Neuroscience, Vol 15, 4102-4108.
[4] Sara R. Jones, Raul R. Gainetdinov, R. Mark Wightman, and Marc G. Caron. Mechanisms of Amphetamine Action Revealed in Mice Lacking the Dopamine Transporter. Journal of Neuroscience, March 15, 1998, 18(6):1979-1986.
[5] Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 2001 Jan;39(1):32-41.
zorn
Bluelighter
deus-
Remember that there are hundreds to thousands of receptors at an individual synapse, and many molecules of transmitter and drug. The receptors will typically not all be continuously occupied, but there will be molecules continuosly binding and unbinding to them. So an amp molecule could bind to a transporter, shuttle out a bunch transmitter molecules, and wander away inside the cell... the transporter might then uptake a molecule or two back inside before binding to another amphetamine molecule and shuttling out more transmitter. You get the idea.
Also, even though we call it a reuptake transporter, it also moves molecules out of the cell from time to time (w/o amphetamine).... the average effect is just to bring them inside.
There are some agents that do bind more or less permanently instead of constantly switching in and out; this is called irreversible binding, but doesn't occur here.
Remember that there are hundreds to thousands of receptors at an individual synapse, and many molecules of transmitter and drug. The receptors will typically not all be continuously occupied, but there will be molecules continuosly binding and unbinding to them. So an amp molecule could bind to a transporter, shuttle out a bunch transmitter molecules, and wander away inside the cell... the transporter might then uptake a molecule or two back inside before binding to another amphetamine molecule and shuttling out more transmitter. You get the idea.
Also, even though we call it a reuptake transporter, it also moves molecules out of the cell from time to time (w/o amphetamine).... the average effect is just to bring them inside.
There are some agents that do bind more or less permanently instead of constantly switching in and out; this is called irreversible binding, but doesn't occur here.
From what I know, you can get high from Parkinson's medication, but not on l-dopa alone. An effective dose (for treating Parkinson's disease) of l-dopa without carbidopa is somewhere in the neighborhood of 6 grams. Fortunately for Parkinson's patients who don't want a liver disease too, someone figured out that l-dopa with carbidopa works quite nicely. With carbidopa, the effective dose of l-dopa is around 200 mg.