MisterJohnson
Greenlighter
- Joined
- May 13, 2013
- Messages
- 28
This is a sort of train of questions, the answers to which I have tried to find UTSE, to no avail, and I was hoping some of you guys might be able to help me out. Even partial answers would be very helpful. This may get a bit long, so please bare with me (yeah, I'm typing naked).
I have tried modafinil and was for a brief period even prescribed R-modafinil, both of which I found to be useful. However, I've recently been plagued with both daytime fatigue and sleepiness. I have recently acquired a bit of adrafinil in powder form as a cost-saving measure, as my job (landscaping/landscape maintenance) requires me to be alert throughout the day, especially on days when I'm the driver. I tried quitting caffeine, or at least minimizing my intake, because the up/crash cycle is not working for me, but I've had to get back on the caffeine, because I cannot find a dose of adrafinil that works for me; I've tried adrafinil from several sources, and they all had the same problem: no dose of adrafinil that I've tried, up to 1200mg(!) has even helped my drowsiness or alertness.
When taking modafinil in the past, I found 300mg to be my optimal dose; with R-modafinil, 200mg served me just as well. I figured something like 400-500mg adrafinil would be equivalent to those doses, given that some of the adrafinil will be converted to the inactive adrafinilic acid [http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.1999.tb00100.x/pdf, pg. 3]. Not so. That study also found that a 40mg/kg dose actually produced a lower plasma concentration after 10hr than the 10mg/kg dose, suggesting a sweet-spot dose, but I titrated up. My first question in this train: does the most-common synthesis of adrafinil produce a 1:1 ratio between the R- and S- enantiomers, or some other ratio? I'm assuming here that my sources' sources use the cheapest, commonest method of synthesis.
Let's assume that the enantiomer ratio of adrafinil is in fact 1:1. When the liver converts adrafinil into modafinil, does it "prefer" one enantiomer over another, say producing a 2:1 ratio of S- and R-modafinil, respectively? From what I've heard, both are active in pretty much the same way, except to my knowledge, that the R- isomer is somewhat more potent, but this study [http://www.ncbi.nlm.nih.gov/pubmed/19391150] seems to indicate that the S-isomer is inactive, at least at the dopamine receptors observed; however, modafinil does not exert its effects solely through dopamine receptors, so the S-isomer is probably only less potent. So are both isomers produced in equal amounts by the liver, or is one "preferred?"
If in fact the S- isomer is "preferred," that may explain why even large doses of adrafinil produced little to no effect.
Another thought that occurred to me was that perhaps I am deficient in one of the enzymes that converts adrafinil into modafinil. Which leads to my third question: what enzymes are involved in this conversion? A deficiency or lack of one may explain the total lack of effects adrafinil has been having one me.
If I cannot solve this problem, I may have to just go ahead and get prescribed modafinil or R-modafinil, but that would have to wait until my current insurance lapses and I can get my ACA-subsidized plan, which I may do anyway, since my subsidy will allow for me to get prescribed modafinil much cheaper than Internet adrafinil. But that won't be for another month or two.
Any help will be greatly appreciated.
I have tried modafinil and was for a brief period even prescribed R-modafinil, both of which I found to be useful. However, I've recently been plagued with both daytime fatigue and sleepiness. I have recently acquired a bit of adrafinil in powder form as a cost-saving measure, as my job (landscaping/landscape maintenance) requires me to be alert throughout the day, especially on days when I'm the driver. I tried quitting caffeine, or at least minimizing my intake, because the up/crash cycle is not working for me, but I've had to get back on the caffeine, because I cannot find a dose of adrafinil that works for me; I've tried adrafinil from several sources, and they all had the same problem: no dose of adrafinil that I've tried, up to 1200mg(!) has even helped my drowsiness or alertness.
When taking modafinil in the past, I found 300mg to be my optimal dose; with R-modafinil, 200mg served me just as well. I figured something like 400-500mg adrafinil would be equivalent to those doses, given that some of the adrafinil will be converted to the inactive adrafinilic acid [http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.1999.tb00100.x/pdf, pg. 3]. Not so. That study also found that a 40mg/kg dose actually produced a lower plasma concentration after 10hr than the 10mg/kg dose, suggesting a sweet-spot dose, but I titrated up. My first question in this train: does the most-common synthesis of adrafinil produce a 1:1 ratio between the R- and S- enantiomers, or some other ratio? I'm assuming here that my sources' sources use the cheapest, commonest method of synthesis.
Let's assume that the enantiomer ratio of adrafinil is in fact 1:1. When the liver converts adrafinil into modafinil, does it "prefer" one enantiomer over another, say producing a 2:1 ratio of S- and R-modafinil, respectively? From what I've heard, both are active in pretty much the same way, except to my knowledge, that the R- isomer is somewhat more potent, but this study [http://www.ncbi.nlm.nih.gov/pubmed/19391150] seems to indicate that the S-isomer is inactive, at least at the dopamine receptors observed; however, modafinil does not exert its effects solely through dopamine receptors, so the S-isomer is probably only less potent. So are both isomers produced in equal amounts by the liver, or is one "preferred?"
If in fact the S- isomer is "preferred," that may explain why even large doses of adrafinil produced little to no effect.
Another thought that occurred to me was that perhaps I am deficient in one of the enzymes that converts adrafinil into modafinil. Which leads to my third question: what enzymes are involved in this conversion? A deficiency or lack of one may explain the total lack of effects adrafinil has been having one me.
If I cannot solve this problem, I may have to just go ahead and get prescribed modafinil or R-modafinil, but that would have to wait until my current insurance lapses and I can get my ACA-subsidized plan, which I may do anyway, since my subsidy will allow for me to get prescribed modafinil much cheaper than Internet adrafinil. But that won't be for another month or two.
Any help will be greatly appreciated.
