Posted by Elizabeth on October 29, 2001, at 10:44:20
In reply to Re: CA rocket fuel; modafinil pharmacology » Elizabeth, posted by SLS on October 29, 2001, at 8:58:42
> I've been feeling less than spectacular, so please forgive my dereliction.
Sorry to hear it. I just thought that maybe you'd missed my question,
> I've explored modafinil well enough to feel confident that it is not at this time considered to be active directly upon dopaminergic neurons.
If it were, do you think that Cephalon would want to know? I don't. It's C-IV, they want it to stay C-IV.
The only relevant data I could find in the PI:
"In vitro, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release." [no information about in vivo activity is provided]
"In addition to its wakefulness-promoting effects and increased locomotor activity in animals, in humans, PROVIGIL produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants. Modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine; modafinil was also partially discriminated as stimulant-like."
The PI lists lots of things that modafinil *doesn't* do, but doesn't include any hypothesis as to what action might be responsible for its effects (in particular, the effects described in the second quotation above). Maybe the dopaminergic-like effects are the result of some action other than dopamine transporter blockade -- but what that mechanism might be is unclear. I want to find out the Kd with respect to the DA transporter because that would allow me to decide for myself whether DA reuptake inhibition is significant at clinically-used doses.
> I'm sure you can find all of the material necessary to assess this for yourself.
As I said, I wasn't able to find out the Kd for modafinil (despite my not-so-vast resources) and I was wondering if you knew it or any other relevant information.
> It probably doesn't hurt too much to occasionally treat the brain as a black-box. Provigil seems pretty safe.
I'm certainly not disputing that. I think it's a fine drug, and probably more effective for ADD, depression, chronic fatigue, etc., than it is for narcolepsy. (In fact, I don't understand why it's marketed for narcolepsy at all -- except, of course, for political reasons.)
-elizabeth
poster:Elizabeth
thread:81334
URL: http://www.dr-bob.org/babble/20011025/msgs/82567.html