Disappointed by Modafil
#31
Posted 29 June 2006 - 02:20 PM
Not sure. I am going to stop for a few days to see if the pain goes away, then retry it again to see if it comes back. If it does come back I may discontinue using it. I am a firm believer to listen to your body when it comes to small pains like this.
#32
Posted 29 June 2006 - 04:33 PM
In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil.
Robertson P, DeCory HH, Madan A, Parkinson A.
Department of Drug Safety and Disposition, Cephalon, Inc., West Chester, Pennsylvania, USA. proberts@cephalon.com
The ability of modafinil to affect human hepatic cytochrome P450 (CYP) activities was examined in vitro. The potential for inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, and CYP4A9/11 by modafinil (5-250 microM) was evaluated with pooled human liver microsomes. Modafinil exhibited minimal capacity to inhibit any CYP enzyme, except CYP2C19. Modafinil inhibited the 4'-hydroxylation of S-mephenytoin, a marker substrate for CYP2C19, reversibly and competitively with a K(i) value of 39 microM, which approximates the steady-state C(max) value of modafinil in human plasma at a dosage of 400 mg/day. No irreversible inhibition of any CYP enzyme was observed, and there was no evidence of metabolism-dependent inhibition. The potential for induction of CYP activity was evaluated by exposing primary cultures of human hepatocytes to modafinil (10-300 microM). Microsomes were then prepared and assayed for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 activities. The mean activities of microsomal CYP1A2, CYP2B6, and CYP3A4/5 from modafinil-treated hepatocytes were higher (up to 2-fold) than those in the solvent-treated controls but were less than those produced by reference inducers of these enzymes. At high concentrations of modafinil (>/=100 microM), the mean activity of CYP2C9 was decreased (up to 60%) relative to that in the solvent controls. Overall, modafinil was shown to have effects on human hepatic CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4/5 activities in vitro. Although effects obtained in vitro are not always predictive of effects in vivo, such results provide a rational basis for understanding drug-drug interactions that are observed clinically and for planning subsequent investigations.
Clinical pharmacokinetic profile of modafinil.
Robertson P Jr, Hellriegel ET.
Department of Drug Safety and Disposition, Cephalon, Inc, West Chester, Pennsylvania, USA. proberts@cephalon.com
Modafinil is a unique wake-promoting agent for oral administration. Its pharmacological properties are distinct from those of other CNS agents, and it selectively targets neuronal pathways in the sleep/wake centres of the brain. After single or multiple oral doses, modafinil is readily absorbed, reaching maximum plasma concentrations at 2-4 hours after administration and pharmacokinetic steady state within 2-4 days. Its pharmacokinetics are dose-independent between 200 and 600 mg/day. The elimination half-life is approximately 12-15 hours, which is largely reflective of the pharmacokinetics of the longer-lived l-enantiomer. Modafinil is primarily eliminated via metabolism, mainly in the liver, with subsequent excretion in the urine. Less than 10% of the dose is excreted as unchanged drug. Metabolism is largely via amide hydrolysis, with lesser contributions from cytochrome P450 (CYP)-mediated oxidative pathways. In patients who are renally or hepatically compromised, the elimination processes can be slowed, and in a similar manner (although to a lesser extent), elimination in the elderly may be reduced due to normal effects of aging. Because modafinil is administered concomitantly with other medications, the potential for metabolic drug-drug interactions has been examined both in vitro and in vivo. In vitro, modafinil was observed to produce a reversible inhibition of CYP2C19 in human liver microsomes. It also caused a small, but concentration-dependent, induction of CYP1A2, CYP2B6 and CYP3A4 activities and suppression of CYP2C9 activity in primary cultures of human hepatocytes. Clinical studies have been conducted to examine the potential for interactions with methylphenidate, dexamfetamine, warfarin, ethinylestradiol and triazolam. The only substantive interactions observed were with ethinylestradiol and triazolam, apparently through induction of CYP3A4, primarily in the gastrointestinal system. Overall, the results of the interaction studies suggest that modafinil has potential to affect the pharmacokinetics of drugs that are metabolised by certain CYP enzymes. Compounds that induce or inhibit CYP activity are unlikely to have major effects on the pharmacokinetics of modafinil. In summary, the results show that modafinil is a moderately long-lived drug that is well absorbed and extensively metabolised.
#33
Posted 30 June 2006 - 04:21 AM
#34
Posted 30 June 2006 - 06:18 AM
regino007, your back ache could be caused by sitting in one position for a long time. Drugs like modafinil can make four hours seem like no time at all, so you may not realize the physical strain you put on your body.
I sit for long periods at a time already. I went ahead and took 200mg today at noon. It always seems the pain hits mostly at night around 11pm or so...........like enough time for the med to make its way through or something.................I'm not going to take it for a few days to see if it stops..............
I've taken a few other things before and never had a pain like this. I started taking this last Sat,by Mon night I was feeling an uncomfortable pain in my lower back.........like in my kidney area.I thought it was the beer drinking I had Sat night but it really hasn't gone away.
#35
Posted 01 July 2006 - 01:47 PM
regino007, your back ache could be caused by sitting in one position for a long time. Drugs like modafinil can make four hours seem like no time at all, so you may not realize the physical strain you put on your body.
I sit for long periods at a time already. I went ahead and took 200mg today at noon. It always seems the pain hits mostly at night around 11pm or so...........like enough time for the med to make its way through or something.................I'm not going to take it for a few days to see if it stops..............
I've taken a few other things before and never had a pain like this. I started taking this last Sat,by Mon night I was feeling an uncomfortable pain in my lower back.........like in my kidney area.I thought it was the beer drinking I had Sat night but it really hasn't gone away.
Hi Regina
I always feel that we have gut feelings ...........that if you feel that an organ may be involved you are probably right [sfty]
You should stop all meds and never drink if you are taking modifanil ... because your liver may not be able to handle it(I know with provigil there is a warning about drinking)
I am not sure of your age but it was a common occurance and that pain is a symptom that I saw with friends when I was younger that got urinary infections and if you also have a problem urinating, infrequent ,feeling a need to urinate and then you can't... Cranberry juice will help flush your kidney, stop meds and alcohol....lots of water
And if that doesnt help you may need to see a doctor because you may need an antibiotic
June
#36
Posted 05 July 2006 - 06:56 PM
I have stopped taking it for a few days and I must say that the pain has not come back. I want to try it again to test to see if that was the cause...........I may wait for now.
Now I have alot of these just sitting around.......................lol
#37
Posted 10 July 2006 - 10:30 PM
It is well established that memory and sleep go hand in hand.
Is it counter productive to stay alert when you dont have the sleep cycles to process, and store?
The wealth of experience on this site should lead to some interesting answers.
#38
Posted 11 July 2006 - 10:08 AM
It is well established that memory and sleep go hand in hand.
Is it counter productive to stay alert when you dont have the sleep cycles to process, and store?
For the long haul, I don't think you'd find much argument in favour of going that route. As you say, it just doesn't mesh too well with what we've seen happen in people undergoing even minor long term sleep deprivation. That said, I don't think anyone can really give much more than a guess about how that's going to hold up with any particular new drug added into the mix. I don't think we really know enough about memory consolidation at this point to speculate too far about what effect a combination of lowered sleep time and altered sleep pattern arising from a drug would be without actual experimentation.
One also has to keep in mind the different needs for an a particular individual, in a particular time, in a particular place. Someone whose main mental task is a day or two of memorising data for an exam whose topic will never come up again is going to have very different needs than another person who has to learn a large amount of new data in a short period of time, and then apply that information in a creative way to some situation.
#39
Posted 11 July 2006 - 02:34 PM
I have not taken any Modalert since July 1st. I must say that I have not had that "pain" since then.
I am going to take it again maybe today and see if that is what has caused it. I'll keep updating when I do.
#40
Posted 28 July 2006 - 05:56 PM
#41
Posted 31 July 2006 - 01:47 PM
[/quote][/quote]
why shouldn't bromocriptine be messed with
#42
Posted 20 August 2006 - 04:05 AM
#43
Posted 21 August 2006 - 07:41 AM
Psychiatry is a medical speciality whose primary goal is to improve people's mental well-being. This can be by managing and improving the symptoms of specific mental illness, as well as assisting people to gain insight into themselves and their relationships with others.
The name derives from the Greek for "healer of the spirit". In the United States, it is practised by people, termed psychiatrists, holding M.D. or D.O. degrees.
While all clinicians encounter patients with mental illnesses and any of them may treat it, psychiatrists specialize in these areas. They are specifically trained in pointing out and medication of abnormal behaviour. Treatment can involve medication, psychotherapy (such as cognitive behaviour therapy, interpersonal therapy, and psychodynamic psychotherapy), and psychosocial interventions. The majority of modern treatments involve medication.
You can get an MD in the US to prescribe you modafinil; and that's exactly what I suggest you try to do...and stop messing around with this questionable international stuff. That should be your last resort. I have filled prescriptions for MANY meds at my local pharmacy written by my doctor. Provigil is the only medicine my insurance company will not authorize for me (no matter how many times my doctor appeals). If you have an organ (or maybe even two) malfunctioning or suffer from some weird genetic defect that makes you metabolise modafinil at some super slow rate, your doctor might be able to figure this out and prevent possible any damage from happening.
Nick Boström says in the clip linked below that the development of drugs that may enhance cognition are a "side effect of drug development." So, when you look for a MD, I suggest you call every one you can (or every one your insurance company works with) and tell them you have tried modafinil and you feel you might have ADD or ADHD. Have you seen a doctor to asses if you might have ADD, or perhaps if you might benefit from these therapies?
http://streaming.oii...6/16032006-1.rm
MDs in the USA (where I know you are) have access to quite a large variety of medicines to treat most disorders effectively. As you may know, cognitive enhancement is not a priority for the FDA; so there are no drug companies developing drugs specifically to enhance cognition --- especially for healthy subjects. Even the "nootropics" sold as dietary supplements in the USA are only sold as such because the US FDA did not reject a prior notification from US supplement companies and they felt they had no inherent toxicity -- or effect (at least that's the case with Piracetam, it seems). No one regulates these products...and they are commonly sold as "food product"...so vendors, by LAW, cannot make claims about nootropics making you "smarter" without taking the risk of getting a visit from the FDA. Similarly, an MD cannot really prescribe you a drug to enhance your cognitive function without possibly getttng sued for malpractice. Most folks who really benefit from such therapies can fit into DSM-IV criteria, so MDs can't get any heat.
#44
Posted 21 August 2006 - 11:43 AM
I felt like I was retaining nothing, short-term memory or concentration seemed to be far below normal. I don't know what modafinil actually does to produce short-term cognitive effects. I feel like it stimulated some process which produced the initial cognitive boost or at least feeling of having increased alertness, but then something became depleted. I drank some tea in the afternoon, but that did not restore cognitive function. Now I have a slight headache. Otherwise, I feel awake and alert, I just don't feel like thinking.
That's interesting, I tend to have the same effect with methylphenidate: alert, but not really feeling like my head wants to think anything complex. I think it goes to show that the meds might overstimulate sites where there's already enough acitivity and the brain doesn't like overactivity which makes you end up with lowered cognition.
#45
Posted 21 August 2006 - 06:34 PM
I think it goes to show that the meds might overstimulate sites where there's already enough acitivity and the brain doesn't like overactivity which makes you end up with lowered cognition.
Having very little knowledge of biology/neurobiology...that's what I too am thinking.
It seems to work for some people though. It still kept me up a while so I guess it could be useful for performing relatively simple or tedious tasks which take a while. But in regards to learning and comprehending new concepts, modafinil was only productive for the first three or four hours, and even then, I am not sure it was really that helpful at all. I have yet to find a one-size-fits all nootropic or brain enhancer. I think I am going to adopt kenj's philosophy and give up all "nootropics" and focus instead on ensuring that there are no limiting factors affecting my mental performance. Limiting factors in terms of diet, exercise, and nutrition. Find a better multivitamin, continue taking anti-aging related supplements, adopt a consistent sleep pattern. I will still keep an eye on cognitive enhancers though. When the stuff becomes mainstream around college science and engineering students and the high-tech crowd, I will definitely look into it. (When the stuff shows up in a Starbucks next to MIT or is advertised right after a Viagra commercial -- assuming the advertisement does not show up in the middle of a NASCAR race :-) -- then I will probably jump on the bandwagon.)
#46
Posted 27 August 2006 - 08:56 AM
That's right where I'm at as well... On the days that I have taken Modafinil by the end of the night when I read I don't comprehend nearly as well. I also would much rather watch a movie on those nights than read (It's usually the opposite).I think I am going to adopt kenj's philosophy and give up all "nootropics" and focus instead on ensuring that there are no limiting factors affecting my mental performance. Limiting factors in terms of diet, exercise, and nutrition. Find a better multivitamin, continue taking anti-aging related supplements, adopt a consistent sleep pattern. I will still keep an eye on cognitive enhancers though.
#47
Posted 31 August 2006 - 01:26 AM
Edited by pbx06, 31 August 2006 - 01:36 AM.
#48
Posted 03 July 2009 - 03:00 PM
I also sell them in the 10 packs if anyone is interested..
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