Stimulants Difference between dopamine agonists and stimulants?

[glab]

Hi,
can somebody explain to me what's the difference is between let's say amphetamines and dopamine agonists like pramipexole?
I know that pramipexole has side effects like daytime sleepiness which stimulants do not have. Why is that? Do stimulants like amphetamines
or ritalin only affect certain DA receptors while dopamine agonists hit ALL DA receptors?
If yes, does this basically mean that stimulants are better than dopamine agonists if you want to increase wakefullness and concentration?
Or can dopamine agonists do the same?

I'd be interested in trying pramipexole against depression cause some doctors use it against depression. But it also seems to have a lot of side effects.
I don't know how much sense it would make to try pramipexole when I have access to dexedrine and ritalin.

 

[Epiper888]

They are totally different. You can't get high off dopamine agonists. Dopamine can do a lot of different things not just make you feel good. Cant really explain the difference but I bet someone else can.

 

[glab]

This doesn't sound good. If an agonist cannot make you feel high then what's it supposed to do for depression?

 

[sekio]

The thing with dopamine receptors is, there's many subtypes of them (just like serotonin receptors, or adrenergic receptors). And the subtypes can have different effects depending on where they are localized in the brain, too.

There are a few dopamine receptor agonists that do activate the subtypes of dopamine receptors responsible for euphoria and stimulant effects, but they are all research chemicals like SKF-82,958 and as far as I know they have never been used in humans. They haven't been used because they have been shown in animal models to cause self-administration, that is, rats will keep redosing if you give them the chance. They also substitute for cocaine and amphetamine. Drugs like pramipexole are not self-administered and don't mimic stimulants so the FDA is way more lenient with them.

Most synthetic dopamine receptor agonists used in medicine were essentially developed to minimize "abusable" side effects for the conditions they are used to treat. For instance, activating certain dopamine receptors can alter the level of horomones like prolactin in your body, and if that's your intended effect then giving someone amphetamine is going to produce a lot of sweatiness, shaking, high blood pressure etc. compared to a selective agent.

 

[AlphaMethylPhenyl]

I think that's a really great question. I do know that euphoria can't be reduced to dopamine though. It also has to do with the ratio of neurotransmitters in various parts of the brain. I would be surprised if parkinsons drugs like the one you stated increases levels of dopmaine in the nucleus accumbens.

 

[Memantine]

D2 and D3 receptors are more widespread in the limbic dopaminergic system. High doses of D2/D3 agonists should give some positive effect on mood. Low doses however block pre-synaptic dopamine autoreceptors resulting in a decreased dopamine synthesis and increased DAT function. In the same way D2/D3 antagonists should block dopaminergic transmission in high doses but enhance it at low doses.

D1/D4 receptors are found more in the striatal dopaminergic system(accociated with PD) i believe but i am not sure.

 

[AlphaMethylPhenyl]

I believe that D2 receptors are more found in the striatum/primitive part of the brain while D1 receptors are more found in the executive part of the brain (i.e. the frontal cortex).

 

[danglesmcgee]

D2 and D3 receptors are more widespread in the limbic dopaminergic system. High doses of D2/D3 agonists should give some positive effect on mood. Low doses however block pre-synaptic dopamine autoreceptors resulting in a decreased dopamine synthesis and increased DAT function. In the same way D2/D3 antagonists should block dopaminergic transmission in high doses but enhance it at low doses.

D1/D4 receptors are found more in the striatal dopaminergic system(accociated with PD) i believe but i am not sure.

a little off topic here, but you seem like the guy to ask .... what exactly do dopamine re-uptake inhbitors do such as methylphenidate... my understanding is that they basically stop the dopamine from being thrown back into the abyss and therefor increase dopamine density in the brain, so methylphenidate doesnt cause any production in dopamine...just kind of "recycles it around" ...am i making sense?

 

[Memantine]

Normally dopamine is released from its storage vesicles in the pre-synaptic neuron so it can deliver its message to the post synaptic neuron. After the message has been delivered the dopamine transporter DAT, wich is located on the pre-synaptic axon, transports the dopamine back to storage vesicles in the axon. Methylphenidate prevents dopamine from being transported back to it's storage vesicle in the pre-synaptic axon, thus leaving the dopamine availible in the synaptic cleft to stimulate the dopamine receptors more.

So to get back at your question, indeed methylphenidate does not cause an increased dopamine production. It blocks the dopamine recycling system.

 

[mike.vick]

a little off topic here, but you seem like the guy to ask .... what exactly do dopamine re-uptake inhibitors do such as methylphenidate... my understanding is that they basically stop the dopamine from being thrown back into the abyss and therefor increase dopamine density in the brain, so methylphenidate doesnt cause any production in dopamine...just kind of "recycles it around" ...am i making sense?

DRI and any RI doesn't "stop dopamine from being thrown back into the abyss" Rather it blocks the pre-synaptic reuptake/reabsorption of dopamine. In other words, it keeps the dopamine in the synaptic gap longer, the synaptic gap is the gap between two adjacent neurons. Usually, some dopamine gets reabsorbed in the pre-synaptic neuron to be recycled. Under drugged-conditions with a DRI, the dopamine gets blocked from reentering the presynaptic neuron and being recycled. This causes the dopamine molecules to be forced enter the post synaptic neuron and continue transmission, albeit to a greater degree then normal conditions.

So therefore, DRI doesn't "recycle around" dopamine, that is what happens under normal conditions, and what is prevented by DRI. Rather, they lead to an increase transmission of dopamine, in the brain and spinal cord.

Animation:

=========) (========
presynaptic.....^..Postsynaptic neuron
.............Synaptic gap..............

 

[Hodor]

This doesn't sound good. If an agonist cannot make you feel high then what's it supposed to do for depression?

What Pramipexole mainly works for (besides Parkinson's/RLS, of course) is anhedonia, i.e. the inability to experience pleasure. Since dopamine receptors are involved in experiencing and seeking pleasure, directly stimulating them via an agonist can sometimes provide relief from this condition. They can also offset the decrease in libido caused by SSRIs.

2 things to consider though:
* even at a minimum dose, the first days on Pramipexole may very well have you feeling somewhat unwell. Cold, nervous, slightly nauseous... these side-effects mostly pass after a few days though
* the drug can also work a bit *too* well, giving you Dopamine Dysregulation Syndrome, causing an increase in compulsive and hedonistic behavior... this can mean anything from "very strong libido" to "compulsively masturbating to gay porn and uploading pics of yourself in drag to fetish forums" to "financially ruining yourself with a gambling addiction". That said, this is probably fairly unlikely in people taking it at low doses as an antidepressant, as opposed to the high doses + L-DOPA that people would take for severe RLS/Parkinson's.

 

[lostie2342]

D2 and D3 receptors are more widespread in the limbic dopaminergic system. High doses of D2/D3 agonists should give some positive effect on mood. Low doses however block pre-synaptic dopamine autoreceptors resulting in a decreased dopamine synthesis and increased DAT function. In the same way D2/D3 antagonists should block dopaminergic transmission in high doses but enhance it at low doses.

D1/D4 receptors are found more in the striatal dopaminergic system(accociated with PD) i believe but i am not sure.

I have medical issues and I am trying to figure out whether it would be safe to take adderall in the AM and a parkinsons dopa agonist in the PM for periodic limb movement (that class of drugs is often prescribed for RLS/PLMD). I'm a bit wary because I already am experiencing the side effects and possible neurotoxicity of longterm adderall use. Logically it seems like I'd be playing with fire to hit my dopamine receptors again, but I could be wrong in this, and that a dopa agonist could repair and rejuvenate the system, and indeed I have such severe PLMD because of adderall wiping out my dopamine. Any insights from you or any other on this board would be greatly appreciated, thanks!

 

[d1nach]

Cant you go to the doctor and get a drug approved for rls?

 

[lostie2342]

Of course, that is the plan. I'm just trying to better understand the pharmacology so I can make an informed decision. People for some reason (maybe people with little experience with actual doctors) assume doctors understand the nuances these things, but generally are completely clueless of the chemistry, and dismissive of any interactions etc. unless explicitly listed somewhere.

 

[sekio]

Dopamine agonists do not "repair" anything, if anything they will make the problem worse.

 

[Captain.Heroin]

The thing with dopamine receptors is, there's many subtypes of them (just like serotonin receptors, or adrenergic receptors). And the subtypes can have different effects depending on where they are localized in the brain, too.

There are a few dopamine receptor agonists that do activate the subtypes of dopamine receptors responsible for euphoria and stimulant effects, but they are all research chemicals like SKF-82,958 and as far as I know they have never been used in humans. They haven't been used because they have been shown in animal models to cause self-administration, that is, rats will keep redosing if you give them the chance. They also substitute for cocaine and amphetamine. Drugs like pramipexole are not self-administered and don't mimic stimulants so the FDA is way more lenient with them.

Most synthetic dopamine receptor agonists used in medicine were essentially developed to minimize "abusable" side effects for the conditions they are used to treat. For instance, activating certain dopamine receptors can alter the level of horomones like prolactin in your body, and if that's your intended effect then giving someone amphetamine is going to produce a lot of sweatiness, shaking, high blood pressure etc. compared to a selective agent.

The drug you listed also hits estrogen receptors. Yikes.

 

[LesFleursDuMal]

The answer to this thread could be broken down by drawing a Venn diagram. Some dopamine agonists are stimulants and some stimulants are dopamine agonists. They don't always indicate the other, in fact, stimulants are more a class of drugs whereas dopamine agonism is a characteristic of mostly just addictive drugs. The reward system plays a part in many different types of drugs though, and also there are some stimulants which lack dopamergenic action and thus lack an addictive profile.