The Corpus Callosum

A while back, I wrote about the new treatment for href="http://en.wikipedia.org/wiki/ADHD" rel="tag">ADHD
that is under
development
, href="http://www.nrpharma.com/products/NRP104.htm" rel="tag">NRP104.
 The original post is href="http://trots.blogspot.com/2005_02_27_trots_archive.html">here.
 In that post, I reviewed the pharmacology of NRP104.
 The basic idea is that the company took an old molecule, href="http://en.wikipedia.org/wiki/Dextroamphetamine" rel="tag">dextroamphetamine,
and tacked a molecule of
onto it.  That renders it inactive, until an enzyme lops off
the lysine.  The point is to try to reduce the potential for
abuse.

NRP104 has moved up the pipeline, and now has href="http://rds.yahoo.com/_ylt=A0geurYAJ0RFBCgBK9lXNyoA;_ylu=X3oDMTEwN3NhaXNsBGNvbG8DZQRsA1dTMQRwb3MDMTEEc2VjA3NyBHZ0aWQD/SIG=157fogedh/EXP=1162180736/**http%3a//www.redorbit.com/news/health/684391/fda_issues_approvable_letter_for_nrp104_lisdexamfetamine_dimesylate_for_the/index.html%3fsource=r_health">gotten
an approvable letter from the FDA.  It also has a
real name now: lisdexamfetamine dimesylate.  It is so new that
it does not even have a Wikipedia page yet!

What is the point of this exercise?  Do we really need another
repackaged version of an old compound?


The answer is yes, but the reason depends on whom you ask.
 Abuse of prescription stimulants is a bit of a problem.
 By href="http://sitemaker.umich.edu/umsarc/files/15-41.pdf">one
estimate (PDF link), about 5.9% of college undergranduates
will take stimulants that were not prescribed for them.  How
much of that is enough of a problem to worry about is subject to
debate, but it indicates that there is a porblem.  

Shire and their partner, New River Pharmaceuticals, have presented data
showing there is less potential for abuse of lisdexamfetamine
dimesylate, compared to dextroamphetamine.  If that turns out
to be the case on the street, so to speak, then it would be an
improvement.  

So if you ask clinicians if there is a need for a new compound, they
would say there is.  That is because no clinician wants to act
as an enabler for someone else’s substance abuse.  

If you ask the pharmaceutical company, the answer is also yes.
 The patent for Adderall has run out.   The other
patented stimulants are running out of patent life.  But if
something new is going to make it to the market, it has to have some
kind of selling point.  A reduced potential for abuse could be
just that.

But how different will lisdexamfetamine really be?  The data
presented by the company show that drug abusers do not like it as well
as regular amphetamine.  They also show that the blood level
of the drug stops going up in proportion to the dose, at doses above
130mg.  So, taking very high doses may not make up for the
delay in attaining peak concentration.  

There are other data avaiable, which are favorable as well.  
The University
of Michigan Substance Abuse Research Center
has on their site
a
PDF
on the subject.  On page 27, there is agraph
showing that nasal insufflation (snorting) results in nearly undectable
blood levels of dextroamphetamine, at least in rats.

Shire is hoping that the DEA gives the drug a rating lower than
schedule II, but it is not yet know if that will be the case.
 The reason that is important, is that prescriptions for
schedule II medications cannot be refilled, and prescriptions cannot be
called in.  It is a nuisance for all involved.  Just
getting rid of the nuisance factor would make the product more popular
with doctors and patients.  From the href="http://www.redorbit.com/news/health/684391/fda_issues_approvable_letter_for_nrp104_lisdexamfetamine_dimesylate_for_the/index.html?source=r_health">press
release:

If NRP104 is approved with a Schedule III, IV or V
classification
or is unscheduled (“favorable scheduling”), Shire will pay New River a
$300 million milestone payment. US operating profit will be divided as
follows: Shire will retain 75 percent of profits for the first two
years following launch, and the parties will share the profits equally
thereafter.

In the event that NRP104 receives a final Schedule
II classification, no milestone payment will be payable by Shire to New
River upon approval. Division of profits will be calculated under an
alternative profit sharing scheme.

If some actual social good comes of it, so much the
better.  The thing is, it is difficult to know what
the abuse potential
really is, until the product has been on the market for a while.
 Personally, I suspect that they will get a favorable
classification from the FDA, but that will be subject to change.
 If the product turns out to be abused widely, the FDA could
reclassify it.

(As an aside for those who like the chemistry of this kind of molecule,
Molecule of the Day has href="http://scienceblogs.com/moleculeoftheday/2006/10/lmethamphetamine_would_you_bel.php">a
post on the related compound, l-methamphetamine.)

Comments

  1. #1 whitewhale
    October 30, 2006

    I don’t think it indicates a problem when 5.9% of college undergranduates take stimulants that were not prescribed for them.

    Clearly, NRP140 is not about reducing the abuse potential of methamphetamines, its about making money in a market that needs drugs.

  2. #2 Joseph j7uy5
    October 30, 2006

    There is some truth to that, but even if the benefit is only a perceived benefit, there is a practical advantage. If NRP104 gets a schedule III or IV classification, it will be a lot more convenient for doctors and patients. Granted, that is not what is motivating the companies that are working on it, but it is worth something.

    Plus, there probably will be some people who tolerate it better that the existing product. Less anxiety, perhaps.

  3. #3 Hyperion
    October 30, 2006

    As an ADHD patient, it would be wonderful to be able to get refills or have my physician call in a precription in an emergency (such as if either he or I were on vacation).

    But as important as the accessibility factor is, the more important issue in my mind is dignity. It is difficult enough to go through life with a neurological disability. It is even more difficult when many otherwise educated and intelligent people believe that it does not exist, or that it is merely a lack of discipline…but to then be treated like a drug addict by my insurance company, to have pharmacists glance at the prescription and immediately announce that they don’t have enough on stock to fill it…to essentially be persecuted for seeking treatment…

    And then even when it is recognized that you have a legitimate medical need for treatment, there’s still the attitude that I should be greatful to be allowed to receive the medication, as if I should just accept that the danger of other people getting high is clearly more important than whether I have the neurological function necessary to remain employed.

    Yeah, I’d say a non-abusable version of dextroamphetamine would be a g_dsend. Is there any indication that they would make a d/l mixed-salt version (ie lis-Adderall), or only a dexedrine-style version (also, XR version or no?)?

  4. #4 Wendy
    November 5, 2006

    I agree with the last post. It is a major pain to have to call in for this every month, fetch the paper prescription, and then get that ‘look’. (I switched pharamcies so I don’t get those looks anymore.)I struggled my whole life with ADD. Once I figured it out, and took my first dose, wow! I was finally like everyone else. (But I kept my quirky sense of humor.)

    Ok, yes, there are people who are abusing it, and a true addict will find another drug to abuse if this one goes away, while 95% of us take it responsibly.

    My question is this. How does this drug affect the liver’s P450 system? I’ve looked for info about this, and can’t seem to find any. (I have a blood disorder that originates in the liver.)

  5. #5 Watt de Fawke
    October 9, 2007

    I’m amazed that a patent was issued for Adderall, as it is merely a mixture of four amphetamine salts with different half-lives. Does Mars, Incorporated, get a new patent if they shift the distribution of colored M&Ms?

  6. #6 len
    August 9, 2009

    I am just starting to find out how hard it is to fill the schedule II drug that I take for add
    It works so well that I hate to change but not having to bother the doc and picking up the perscription every time would be good. Well here I go to start my journey on what works and what doesnt.

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