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  • N&PD Moderators: Skorpio | someguyontheinternet

direct dopamine agonist?

Blood pressure is controlled in the brain? Some times it is. But not when your inject adrenaline or dopamine its not. IVed dopamine will have almost no access to the CNS.
 
Tyrosine, DLPA and LDPA, and some RX only medications used for alzheimers called Levapoda or Carpadopa, depending on brand name, are all dopamine agonists. Levapoda is a major dopamine agonist, it'll do whatever you're looking for a dopamine agonist to do ;)

I personally take like 3 grams of tyrosine a day, because I, too, have had this exact same question. I need more dopamine because I am addicted to amphetamines and used to be addicted to cocaine and my dopamine levels aren't what they used to be. Tyrosine is a decent agonist (it also is a norepinephrine agonist), but you have to take it correctly. Take Tyrosine on a completely empty stomach, like in between lunch and dinner. Reason you must take it like this for it to have an effect is that it is an amino acid, and the plethora of other amino acids contained in food compete with the tyrosine for their designated purposes in the brain. Tyrosine is a non-essential amino acid, and is therefore one of the last to get used.

Before you do whatever dopamine-inducing recreational substance you plan on doing, take tyrosine on a totally empty stomach and take a little bit of vitamin C and some B-complex to assist in its efficiency in dopamine stimulation. (B complex is especially important, and will maximize the amount of tyrosine converted into dopamine significantly. Then i'd suggest not eating for about another 2 hours, and then doing whatever you were going to do. DLPA and LDPA are similar to tyrosine, but i have found tyrosine to be the most effective.

(Barring Levapoda, of course, hehe!) Get some of that shit and do two lines of coke and your concept of what heaven is like will be re-adjusted :) )
 
>>Tyrosine, DLPA and LDPA, and some RX only medications used for alzheimers called Levapoda or Carpadopa, depending on brand name, are all dopamine agonists. Levapoda is a major dopamine agonist, it'll do whatever you're looking for a dopamine agonist to do>>

Er...these supplements increase dopamine activity in that they serve as metabolic precursors, and will in that way increase the amount of dopamine synthesized in teh brain. I was axe-ing about DIRECT dopamine agonists.

>>Dopamine is a pretty good dopamine receptor agonist.

I think it's likely that any drug that is an agonist of the dopamine receptor will increase the reuptake of dopamine through negative feedback (in an attempt to re-establish equilibrium)>>

Intercranial injection, anyone? You raise a good point, although in my question I was concerned about inhibition of reuptake, not facilitation.

ebola
 
>>Rather than use a new reply for an off-topic q: It's not really a song, it's just the good Captain playing with words between the tracks on Trout Mask Replica>.

word. when I saw your name, I was thinking "A squid eating dough in a poly-ethylene bag!"
 
To my knowledge, all an agonist is is anything which stimulates the production of a neurotransmitter, which, in this case, happens to be dopamine. Would tyrosine not then be a dopamine agonist?

I understand that levapoda is another story, but let's just stick with tyrosine for now.

And, although off topic, after you respond to that question, would that mean that 5-HTP is NOT an agonist to serotonin?
 
>>To my knowledge, all an agonist is is anything which stimulates the production of a neurotransmitter>>

this is actually not entirely correct. The definition is broader than that. an agonist for a particular endogenous ligand is a chemical that increase the effect of receptors for that ligand. One way to increase the effect of that receptor is to ingest a chemical which increases the synthesis of that ligand, so, yes, l-dopa is an agonist of sorts. I am, however, concerned with only DIRECT agonists here. That is, chemicals that that increase the effect of a particuarly receptor (in this case, dopaminergic) by fitting into that receptor in much the same way as the neurotransmitter itself would.

ebola
 
An agonist is any drug that increases the effects of a neurotransmitter, whether directly, by inhibition of reuptake, mimickry of the neurotransmitters chemical structure or release of said neurotransmitter.

There are many D2 agonists out there. Cocaine (blocks DA's reuptake), methamphetamine (releases DA), MDMA (mimicks the chemical structure of DA) and nicotine (a direct DA agonist). Even caffeine is a mild DA agonist.
 
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If you will please refer to the topic and first post, I said DIRECT agonist with a lack of agonism via other means.

ebola
 
levidopa, carbidopa, and the original question

Just to clarify: Levodopa is L-dihydroxy-phenylalanine or ortho-hydroxy-tyrosine (essentially, tyrosine with a hydroxy group adjacent to the one already present on the phenyl ring) and it is a direct precursor to dopamine. levodopa is analogous to 5-HTP in that only a decarboxylation step is necessary to produce either dopamine or serotonin, respectively. Unfortunately, levodopa is almost entirely decarboxylated in the periphery, which means that taking levodopa alone (except in massive doses) will only minimally elevate DA levels in the CNS. For levodopa to be clinically efficacious, it must be administered with carbidopa, a peripheral decarboxylase inhibitor (peripheral because it does not cross the blood brain barrier).

As to the original question, it is unlikely that anyone will ever isolate a substance that acts on the mesolimbic dopamine pathway alone. Nature doesn't wast things too often, so if she can use one receptor subtype in two pathways, she probably will, so it's unlikely that you will find a receptor subtype exclusively inhabiting the DA ventral tegmental (VTA) ganglion.

Keep in mind that to activate the pathway from its point of initiation (ie, in the midbrain ganglion), one should not necessarily administer a classic DA agonist. In fact, amphetamine inhibits the firing of DA neurons in vitro (see reference below) presumably by evoking Ca-independent release of DA which binds to autoreceptors in the VTA. Many other transmitter receptors reside on the VTA cells bodies, which is why opiates, nicotine, alcohol, benzos, etc., all excite the mesolimbic pathway. When you take amphetamine, you are not "lighting up" the pathway in this manner: you are causing DA release from terminals at the end of the pathway...if this is confusing, let me know.

Reference: "The Biochemical Basis of Neuropharmacology" by Cooper, Bloom, and Roth.
 
>>Keep in mind that to activate the pathway from its point of initiation (ie, in the midbrain ganglion), one should not necessarily administer a classic DA agonist. In fact, amphetamine inhibits the firing of DA neurons in vitro (see reference below) presumably by evoking Ca-independent release of DA which binds to autoreceptors in the VTA. Many other transmitter receptors reside on the VTA cells bodies, which is why opiates, nicotine, alcohol, benzos, etc., all excite the mesolimbic pathway. When you take amphetamine, you are not "lighting up" the pathway in this manner: you are causing DA release from terminals at the end of the pathway...if this is confusing, let me know.>>

This makes sense, but it is really shattering much of what I've learned thus far. :)

so does this, in part, account for why these direct dopamine agonists are not popular drugs of ...er...recreation? Or is significant nor-epi' action needed for that extra "kick"?

ebola
 
...oh...and just to check that I understand your explanation, amphetamine is fun not simply because of widespread dopamine agonism, but because it causes a dopamine release from terminal buttons ending at nucleus accumbens, thus increasing the firing of THESE neurons in particular.

ebola
 
It shouldn't have shattered much ebola. Amphetamine increases the activation of dopamine receptors. Thats the important part, (theoretically). It does so by releasing dopamine, as against directly binding to dopamine receptors.

Meanwhile, dopamine may or may not 'excite' neurons. It depends on the receptors, and what intracellular machinary is located around these receptors.
 
>>It shouldn't have shattered much ebola. Amphetamine increases the activation of dopamine receptors. Thats the important part, (theoretically). It does so by releasing dopamine, as against directly binding to dopamine receptors.>>

but...as the previous poster has mentioned...it is the location of dopaminergic release that matters. In my education, it was presented as though dopamine agonism anywhere in the mesolimbic dopamine pathway would get the "pleasure circuit" going. eh...i have my own pharmacological issues that are hindering me from deftly comprehending the logic here....so until later...

ebola
 
Amphetamine will cause DA release nonspecifically wherever there is a DA terminal. Therefore, it's wrong to say that all of the subjective effects of the drug are due to mesolimbic DA. As "students of pharmacology," we want to be able to say, unequivocally that "this causes that," or whatever. Unfortunatley, everything is connected to everything else, and in the case of DA, there are at least nine distinct DA pathways including the mesolimbic pathway.

That said, it's always fun to speculate. It may be (and now I'm speculating) that the majority of the subjective effects of amphetamine can be resolved to increaed mesocortical DA activity, and that the mesolimbic circuit simply reinforces the behavior. If this were the case, then blocking activity in the nucleus accumbens would reduce the addictive potential of the drug without reducing the drug's positive experience. This is unlikely, however, because many of the possitive affect changes caused by amphetamine (increased self-esteem, euphoria) are tied to the limbic system.
 
Ah well the idea of a pleasure circut is largely bullshit anyway...

But yes, of course the location of the dopamine release is important. If its released in the striatum it'll effect movement and in other places, other things... whatever activity that place regulates, dopamine release there will effect that activity.
 
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