Comparing impacts of modafinil, cocaine and amphetamines on dopaminergic neurotransmission

[loamyguy]

I'm a long-term stimulant addict trying to figure out this mysterious drug armodafinil that I've just been prescribed to help with amphetamine withdrawals...

I understand that Modafinil (and its enantiomers to different degrees) bind to the DAT. Is this the only way modafinil acts on dopamine?

Armodafinil really does feel like a stimulant for me (though I know it isn't classed as one). It really scratches my the itch I have after years of prescription amphetamine abuse. I'm just coming off of vyvanse and it completely eradicates the physical cravings and withdrawal symptoms. I know modafinil is doing a lot more beyond dopamine, but my first thought was that this experience is coming from its ability to increase synaptic dopamine.

Am I off base? One way to look at it would be to compare it to cocaine, a potent dopamine reuptake inhibitor with a high affinity for the DAT. Cocaine is obviously more of a thrill ride than modafinil, but even, now that I'm taking 250 mg armodafinil as prescribed, the effects have unmistakable shades of amphetamines and cocaine. Or maybe that's in my head... Can anyone point me to a stat or figure compares the dopamine reuptake inhibition of modafinil to that of cocaine? Is it as simple as comparing affinity for DAT?

I'm questioning the idea that modafinil is a good medical approach to stimulant abuse disorder. The thing that would really help would be a comparison of synaptic dopamine levels in different parts of the brain from therapeutic doses of amphetamine salts and modafinil. If you've read through this you can probably tell I'm not an expert on this stuf, so... is that type of info out there? Can you point me to any studies that might help me get to the bottom of all this?

 

[plumbus-nine]

Afaik the -dafinils bind only very weakly to the DAT and the primary mechanism is either histaminergic or something else of which I forgot the name. Interesting that for you modafinil substitutes for amphetamine, my experience was a dysphoric jitteryness but maybe it's just me. I found it to be nothing like amphetamine but I'm also weird in that I only tolerate certain low doses of stimulants, if I go too high I get anxiogenic effects after a while when too much of the dopamine gets metabolized to norepinephrine maybe.

Edit: It's also a D2 receptor partial agonist, maybe that's what you benefit from. Did you ever try memantine? It's said to reverse some of the tolerance to stimulants.
Modafinil even works when dopamine is depleted. This speaks for an independent mechanism but still maybe it's the mechanism on DA which helps you. I'm not against substitution and when using a weaker compound your system will still recover to some degree.

 

[negrogesic]

Can anyone point me to a stat or figure compares the dopamine reuptake inhibition of modafinil to that of cocaine? Is it as simple as comparing affinity for DAT?

Sure, here's a comparison:



As you can see modafinil is quite low potency. Even still it isn't a simple comparison since modafinil interacts with the DAT in a somewhat different manner than cocaine.

 

[Skorpio]

Sure, here's a comparison:



As you can see modafinil is quite low potency. Even still it isn't a simple comparison since modafinil interacts with the DAT in a somewhat different manner than cocaine.

This

Affinity is never the whole answer when looking at a drug's effects. It only measures binding at the target site. Look at efficacy (measure of how much response the drug can produce) data in tandem with affinity for the whole picture.

 

[plumbus-nine]

Cocaine isn't that high in potency either but guess many will agree that it's a beast of its own. Never had really pure coke though, maybe it is more mellow than I'd imagine it to be. Potency/affinity only gives a hint about the required dosages, not more imo.