Shown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by Geezer on June 13, 2003, at 22:19:05
The following is direct from the package insert that comes with Provigil:
"Modafinil is not a direct-or indirect-acting dopamine receptor agonist and is inactive in several in vivo preclinical models capable of detecting enhanced dopaminergic activity. In Vitro, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. In a preclinical model, the wakfulness induced by amphetamine, but not modafinil, is antagonized by the dopamine receptor antagonist haloperidol."Question: Does this mean Provigil is a dopamine antagonist? I don't understand the "haloperidol" part. I do understand amphetamine is both a dopamine agonist and antagonist with a similar adrenergic action.
I am Bipolar II taking 250mg of Lamictal, Prozac 15mg. and 1.5 Klonopin (similar to the cocktail employed by "Colin the Crazy"-wink). My problem - I have taken 200mg. in a single dose, 200mg. devided dose, 400mg. single dose and devided doses of 200mg. each. The results are always the same - I feel great for 4 hours then hit a very disphoric, rebound depression. There is no mania just a very bad flu like feeling that requires a nap and 0.5 of Klonopin to correct the situation.
Since plazma concentrations are reached at "2 - 4 hours" could I be tripping the switch for a mood change at the 4 hour time range? What would you think of trying 50mg. single dose for a week (steady state reached in 2-4 days) then going to 100mg if no problems occur. I have to do something about the atypical depression and higher doses of Lamictal don't seem to help.
Thanks,
Geezer
Posted by avid abulia on June 13, 2003, at 23:44:38
In reply to Provigil Q. Dark Lord Mitch et al, posted by Geezer on June 13, 2003, at 22:19:05
no, what it means is that modafinil does not work on the dopaminergic system to provide it`s wakefulness promoting effects, i.e. you can still have it work for you even if you are taking an antipsychotic.
you might try that slow titration, it may work... but it is postulated that modafinil has its effects primarily through indirectly increasing glutamate and decreasing gaba release, and if klonopin helps correct your problem with it then it probably is not the right drug for you. depression is frequently linked to low levels of gaba, and nmda-type glutamate receptor antagonists or partial agonists (i.e. sort of like a dimmer switch rather than just turning the light out completely) have recently gotten some attention as putative antidepressants--nomifenisine is one such drug, i believe.
~AA
Posted by Ritch on June 13, 2003, at 23:55:39
In reply to Provigil Q. Dark Lord Mitch et al, posted by Geezer on June 13, 2003, at 22:19:05
>...In a preclinical model, the wakfulness induced by amphetamine, but not modafinil, is antagonized by the dopamine receptor antagonist haloperidol."
>
> Question: Does this mean Provigil is a dopamine antagonist? I don't understand the "haloperidol" part. I do understand amphetamine is both a dopamine agonist and antagonist with a similar adrenergic action.
No, Provigil doesn't appear to be a dopamine antagonist (based on that info-also remember that is a "preclinical model" - which means it may be inaccurate), what it intends to convey is.. if you give somebody amphetamine (which *does* act at the D2 receptor as an agonist) and they experience alertness from it-and then you administer haloperidol (Haldol-a known and very potent D2 *receptor* antagonist) it *will* interfere with the alertness that is provoked by the administration of amphetamine-but ooops that would be "clinical". Provigil's mechanism *supposedly* only works to block the reuptake of dopamine in the synapse and doesn't work on the DA receptor directly either as an antagonist or agonist. So someone who is experiencing increased alertness from Provigil shouldn't (according to this statement) find Provigil's effect on alertness subdued by administering haloperidol. Why didn't they express the results of a "clinical" study with subjects..??> I am Bipolar II taking 250mg of Lamictal, Prozac 15mg. and 1.5 Klonopin (similar to the cocktail employed by "Colin the Crazy"-wink). My problem - I have taken 200mg. in a single dose, 200mg. devided dose, 400mg. single dose and devided doses of 200mg. each. The results are always the same - I feel great for 4 hours then hit a very disphoric, rebound depression. There is no mania just a very bad flu like feeling that requires a nap and 0.5 of Klonopin to correct the situation.
>
> Since plazma concentrations are reached at "2 - 4 hours" could I be tripping the switch for a mood change at the 4 hour time range? What would you think of trying 50mg. single dose for a week (steady state reached in 2-4 days) then going to 100mg if no problems occur. I have to do something about the atypical depression and higher doses of Lamictal don't seem to help.
>
> Thanks,
>
> GeezerI know they are in Phase II with this med for bipolar depression. If you are getting dysphoria with it-I'm worried about its utility. It might be possible to take smaller doses more frequently as an experiment. What about 50mg 4x daily? If you want to experiment...
Posted by avid abulia on June 14, 2003, at 11:52:19
In reply to Re: Provigil Q. Dark Lord Mitch et al » Geezer, posted by Ritch on June 13, 2003, at 23:55:39
my personal experience was that taking modafinil with geodon (a D2/D3/D4 antagonist, in that order of affinity) was that it was effective for ADhD without effecting my tics, but it made me pretty sleepy, which geodon didn`t do on its own. my p-doc didn`t want to keep prescibing it long enough for me to know if it would help depression, though, because it was sedating me so badly. who knows why, maybe i`m just a babbling psycho or something ;)
Posted by Geezer on June 14, 2003, at 13:45:19
In reply to Re: Provigil Q. Dark Lord Mitch et al » Geezer, posted by Ritch on June 13, 2003, at 23:55:39
Thanks Mitch,
First, hope you were not offended by the "Dark Lord" tag awarded by Colin ( he is such a rip...much better than CBT ). Thank you for the explanation, I do understand things much better now. Your "pre-clinical" - "clinical" comment did not go unnoticed. Since there is no "empirical science" involved at all in psychiatry (even double blind testing is measured with psychological tests = anecdotal, subjective result). Thank you for helping me understand.
Geezer
Posted by Ritch on June 14, 2003, at 15:17:53
In reply to Re: Provigil Q. Dark Lord Mitch et al » Ritch, posted by Geezer on June 14, 2003, at 13:45:19
> Thanks Mitch,
>
> First, hope you were not offended by the "Dark Lord" tag awarded by Colin ( he is such a rip...much better than CBT ). Thank you for the explanation, I do understand things much better now. Your "pre-clinical" - "clinical" comment did not go unnoticed. Since there is no "empirical science" involved at all in psychiatry (even double blind testing is measured with psychological tests = anecdotal, subjective result). Thank you for helping me understand.
>
> GeezerOH no I wasn't offended at all, I thought it was pretty funny actually. I had read those statements from the prescribing info for Provigil before and hadn't really thought about it until I read your post. What utility does that statement about the "pre-clinical model" really have for a prescribing physician other than a marketing technique ??
Posted by Caleb462 on June 14, 2003, at 16:27:54
In reply to Provigil Q. Dark Lord Mitch et al, posted by Geezer on June 13, 2003, at 22:19:05
Just to clarify a few things... amphetamine is NOT a D2 agonist. Amphetamine causes a large-scale release of dopamine however, which is why a dopamine antagonist can block the effects of amphetamine.
Posted by colin wallace on June 14, 2003, at 18:32:43
In reply to Re: Provigil Q. Dark Lord Mitch et al » Ritch, posted by Geezer on June 14, 2003, at 13:45:19
Geezer,
Much to learn have you.
Speak the name Dark Lord in vain must you not...only to dark side lead you to will it.
Feel every ripple in force can he.Much anger on that path is there.Protect you not will valproate...Yoga.
Posted by Geezer on June 14, 2003, at 20:05:04
In reply to Re: Provigil Q. Dark Lord Mitch et al » Geezer, posted by colin wallace on June 14, 2003, at 18:32:43
> Geezer,
>
> Much to learn have you.
> Speak the name Dark Lord in vain must you not...only to dark side lead you to will it.
> Feel every ripple in force can he.Much anger on that path is there.Protect you not will valproate...
>
> Yoga.Colin ya nut. Have you been smoking those funny cigs. again? By-the-by, I tried that valproate stuff up to 1500mg........it turned me into a fire hydrant. If I can turn up one of those nifty sun flower hats like Dr. Bob's I am going to send it to you.
Geezer
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