![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by ed_uk on November 20, 2004, at 20:37:54
Lofepramine is a popular antidepressant in the UK, I've taken it for quite a while with good results. In many countries it is not available, I don't know why. I do know it's not on the market in the US.
Is lofepramine currently available where you live? Was it ever available? Was it withdrawn from the market?
Ed
Posted by SLS on November 20, 2004, at 21:39:40
In reply to Lofepramine: is it available where you live?, posted by ed_uk on November 20, 2004, at 20:37:54
> Lofepramine is a popular antidepressant in the UK, I've taken it for quite a while with good results. In many countries it is not available, I don't know why. I do know it's not on the market in the US.
>
> Is lofepramine currently available where you live? Was it ever available? Was it withdrawn from the market?
>
> Ed
Hi Ed.I might be wrong about this, but I think lofepramine is acting as a prodrug for desipramine. It is therapeutically inert, with desipramine being the active metabolite.
- Scott
Posted by ben on November 21, 2004, at 1:20:16
In reply to Lofepramine: is it available where you live?, posted by ed_uk on November 20, 2004, at 20:37:54
> Lofepramine is a popular antidepressant in the UK, I've taken it for quite a while with good results. In many countries it is not available, I don't know why. I do know it's not on the market in the US.
>
> Is lofepramine currently available where you live? Was it ever available? Was it withdrawn from the market?
>
> EdIt is available in Switzerland. Check out an international pharmacy to buy it there.
Ben
Posted by Jonathan on November 21, 2004, at 6:05:44
In reply to Re: Lofepramine: is it available where you live?, posted by SLS on November 20, 2004, at 21:39:40
> I might be wrong about this, but I think lofepramine is acting as a prodrug for desipramine. It is therapeutically inert, with desipramine being the active metabolite.
If I remember correctly, the following review paper contains a table giving the affinities of lofepramine, desipramine, maprotiline and nortriptyline for the noradrenaline and serotonin transporters, alpha-1, alpha-2 and beta noradrenoceptors, H1 histamine and M1 acetylcholine receptors (but not 5HT-2A/C or any other serotonin receptors, disappointingly):
N. Brunello et al. (Oct 2002) The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. European Neuropsychopharmacology, 12(5), 461-475.
http://dx.doi.org/10.1016/S0924-977X(02)00057-3Unfortunately, I no longer have free access to this journal, and wouldn't advise anyone to pay $30 to download it in case I'm mistaken: the table could be in an entirely different paper! Perhaps your uni subscribes to the journal, Ed, or gives you free electronic access via Athens?
Uniquely for a teriary amine TCA, lofepramine has no significant effect on serotonin reuptake. As far as I can recall, its receptor affinity profile (from the above paper) is very similar to desipramine's, more similar than either profile is to nortriptyline's, for example. Lofepramine is *not* therapeutically inert - it's as ert as desipramine ;)
One pharmacological target molecule that can 'tell the difference' between desipramine and lofepramine is the fast sodium channel in heart muscle. Whilst desipramine blocks this ion channel at a concentration not far above the therapeutic range, accounting for this drug's cardiotoxicity and narrow therapeutic margin, lofepramine doesn't block it until a ten times higher concentration is reached.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7342685
You are still correct, Scott, that most of lofepramine's therapeutic effect is due to its active metabolite, desipramine. Almost every molecule of a therapeutic dose of lofepramine is converted in the liver into a molecule of desipramine; the blood plasma half-life of lofepramine is about five hours at therapeutic or lower concentrations. Desipramine is removed about five times slower than it is produced, with an elimination half-life of about 25 hours (subject to wide variation due to genetics and drug interactions). This means that, if someone took lofepramine by continuous infusion instead of in discrete 70 mg tablets, so that the concentration of it remained constant throughout the day, then the steady-state concentration of desipramine in his/her system would be five times that of lofepramine: more than 80% of lofepramine's therapeutic action is due, not to the drug itself, but to its active metabolite desipramine.
At higher-than-therapeutic concentrations of lofepramine, the enzyme which converts it to desipramine saturates; the rate of production of desipramine increases little and its concentration remains in the safe, non-cardiotoxic range.
I think desipramine was withdrawn in the UK about five years ago. Even before that, it was seldom prescribed: about 6000 out-patient prescriptions in England (pop. 50 of the UK's total 60 million) compared with 150 times that number for lofepramine, our third most popular TCA after dothiepin (another British oddity) and amitriptyline. To put those figures further into perspective, an NHS patient in the late 1990s was twice as likely during treatment to be bitten by a leech (Hirudo medicinalis - about 12000 prescriptions per year) as given desipramine!
Sources:
http://www.parliament.the-stationery-office.co.uk/pa/cm199798/cmhansrd/vo980720/text/80720w15.htm (scroll down)
http://www.telegraph.co.uk/health/main.jhtml?xml=%2Fhealth%2F2004%2F04%2F12%2Fhleech12.xml
Posted by SLS on November 21, 2004, at 7:07:55
In reply to Lofepramine is a pro-drug, but not inert » SLS, posted by Jonathan on November 21, 2004, at 6:05:44
Hi Jonathan.
Thanks for such a wonderful review of lofepramine!
- Scott
Posted by ed_uk on November 21, 2004, at 7:28:21
In reply to Lofepramine is a pro-drug, but not inert » SLS, posted by Jonathan on November 21, 2004, at 6:05:44
Hi Jonathan,
Thank you for the excellent information.
You're right about desipramine being withdrawn, it wasn't very popular. GPs here prescribe dothiepin nearly as much as fluoxetine!
Do you live in the UK? Have you ever taken lofepramine?
Lofepramine is very popular among psychiatrists because of the low risk of overdose compared with other TCAs. Pdocs here tend to use amitrip for sleep rather than depression.
From Lundbeck Psychotropics....'Lofepramine.....Extensive first-pass metabolism to desipramine. Mean plasma half-life approx. 5 hours. Main metabolite is desipramine. Withdrawn in may countries.'
Basically, I would like to know why lofepramine was withdrawn in some countries. Was it just because it wasn't very popular? There have been rare reports of hepatotoxicity with lofep, I wondered whether this was responsible.
A message to everyone...
Was lofepramine withdrawn in your country? Do you know why?All the best...
Ed
Posted by ed_uk on November 21, 2004, at 8:06:05
In reply to Re: Lofepramine, posted by ed_uk on November 21, 2004, at 7:28:21
Hi again Jonathan,
I forgot to say that I do have an Athens password so I'll look at the article you mentioned. In fact, I think I might have seen it before :-)
Regards,
Ed
Posted by darkhorse on November 22, 2004, at 8:07:49
In reply to Re: Lofepramine, posted by ed_uk on November 21, 2004, at 7:28:21
Lofepramine was also withdrawn from Austria years ago..
Adam
Posted by ed_uk on November 22, 2004, at 11:00:45
In reply to Re: Lofepramine, posted by darkhorse on November 22, 2004, at 8:07:49
Hi Adam!
Do you have any idea why it was withdrawn in Austria?
Ed.
Posted by darkhorse on November 24, 2004, at 5:25:52
In reply to Re: Lofepramine, Adam and Austria » darkhorse, posted by ed_uk on November 22, 2004, at 11:00:45
> Hi Adam!
>
> Do you have any idea why it was withdrawn in Austria?
>
> Ed.I'm afraid not.
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.