Why drugs like budipine which work mainly on non dopamine route are forgotten even though there are so much research proving its effectiveness and safety?
I site below only 2 out of many other papers.
Imad


J Neural Transm Suppl. 1999;56:83-105.

Multiple mechanisms of action: the pharmacological profile of budipine.
Eltze M.

Abstract
Four major components of the mechanism of action have been identified for the antiparkinsonian drug budipine up to now. 1) The primary action of budipine is an indirect dopaminergic effect as shown by facilitation of dopamine (DA) release, inhibition of monoamine oxidase type B (MAO-B) and of DA (re) up-take and stimulation of aromatic L-amino acid decarboxylase (AADC), which in sum might be responsible for enhancing the endogenous dopaminergic activity. 2) Radioligand and functional studies at the N-methyl-D-aspartate (NMDA) type glutamate receptor characterize budipine as a low-affinity, uncompetitive antagonist with fast kinetics and moderate voltage-dependency at the phencyclidine (PCP) binding site, comparable to that observed with amantadine, thereby counteracting an increased excitatory glutamatergic activity. 3) The antimuscarinic action of budipine, verified by functional and binding studies at native muscarinic M1-M3 and human recombinant m1-m5 receptor subtypes in vitro, is up to 125-fold weaker than that of biperiden and corresponds to its approximately 100-fold lower potency to cause experimentally-induced peripheral antimuscarinic effects and explains only part of its high potency, which equals biperiden, to suppress cholinergically evoked tremor. 4) An additional inhibition of striatal gamma-aminobutyric acid (GABA) release by budipine may be beneficial to suppress an increased striatal GABAergic output activity. The contribution of other observed effects to the therapeutic action of budipine, i.e. weak stimulation of noradrenaline and serotonin release, binding to brain sigma1 receptors and blockade of histamine H1 receptors, is not yet clear. By means of these multiple mechanisms, budipine might correct the imbalance of striatal output pathways by restoring DA levels in the striatum, and positively influence the secondary changes in other transmitter systems (glutamate, acetylcholine, GABA) observed in Parkinson's disease.

PMID: 10370904 [PubMed - indexed for MEDLINE]
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Budipine in Parkinson's tremor
Heinz Reichmann
Abstract
It is generally accepted that patients with a tremor-dominant type of idiopathic Parkinson's disease progress more slowly than the ones with the rigid-akinetic type. On the other hand successful treatment of Parkinsonian tremor is a challenge. German neurologists use anticholinergics, budipine, β-blockers, clozapine, dopaminergic substances and for most severe cases deep brain stimulation. Budipine is an enigma because its main mode of action is still unknown, although it is mostly listed under glutamate antagonists. There is however no other anti-Parkinsonian drug available with such a broad spectrum of action as shown for budipine. Budipine has been studied in open and double-blind studies as monotherapy and adjunct therapy. In both instances the drug showed beneficial effects to the patients. It may well be that the non-dopaminergic mode of action of budipine is helpful even for patients who are on stable medication. When 3 years ago reports on budipine-induced prolongation of the QT interval in the ECG emerged larger trials were stopped and nowadays there are strict rules on how to use budipine. Nonetheless, budipine in our hands is a most useful and safe drug to treat tremor and other main symptoms of Parkinson's disease.
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Isn't this supremely frustrating? My doctor informed me how many more drug options for PD exist in other countries and says hold up here is FDA. I understand the need for safety and standards but when it is an already well-established drug?!? Plus used for years in other counties where there is an historical record of use? I don't get it other than that there is no "sponsor" (meaning pharmaceutical corp owning it or re-marketing it for profit) behind it for the FDA to approve it for off-label use. Meaning it is about profit; there is no patent to be file, no high priced designer drug, and no monopoly.

Is there anyone who knows the pharma trade and FDA to explain why this happens? Or maybe given its success in other countries why doctors here won't prescribe it off label? ...besides malpractice threat?

Laura

Imark, does budipine have a market name like nortriptyline is Pamelor, etc.
do you know if it is approved in the US?

Laura,
"Thou shalt not sell a treatment in the USA previously approved in Europe without conducting double blinded trials with a placebo !"

Does that include sham surgery?

"it does"
The FDA has spoken. Reasoning is not required. Best example i can think of is duodopa . I"m sure there are enough recipients in Euope 10 [well we keep saying 10 but it's probably been 15 now] years into the use of this treatment in Europe . Perry Cohen consulted for them at one point and helped to arrange some of the communications.

It's been taking several years of unneutral time. I used to think that it would be the one for me and i've read about great changes in the partcipants. I've never seen one up close but refilling it seems daunting for two not quite functioning hands. I asked the company at a PAN conference and then again unfortunately at the following year's conference.. Both times they made cracks about the FDA; one rep said ,"I don't understand them."

This trial protocol has killed several promising treatments at phase II and what are they going to do if duodopa fails phase 2? Ignore the potential when it's already on the market outside the USA? Maybe they have finished phase 2.

I wonder how many sub types are being cateforized from the intake information..I'm going to call somebody and find out or please post if you know anythng.

T0 the participants in the duodopa trial -- please update us as specifically as you can. That request is now global. maybe we could collect some data and compare it to what the doctors are thinking. This trial is unique because it's been in use already. There is a group exchanging information in the clinical trials subforum...putting out an all call for anyone in the trials or who takes it in Europe . Altho there will be questions for the participants, please tell us what you can.[are permitted].

you can go right to the heard of the matter and tell us if:

it works

it is better than oral meds were

was it worth the time, energy and risk?

are you getting it after the trials finished as compassionate use. I can't see changing and adjusting to something successfully, getting your life back, and then taking it away.GDNF all over again. A contributing factor was the pump/catheter that functioned so well in the UK was not FDA approved. Theyh used one from medtronics.

you can sleep on it

other potential things participants could pass on if permitted:
let us know if:

pump is a nuisance or painful? infections easily avoided?

is it easy to refill for pwp with our degree of fine motor difficulty?

has it changed your life ? how so?

does it give you nausea?

will the placebo participants be allowed in phase 3?

This one should be a no brainer to figure out if you've gotten the real thing. IS that true? Don't they think a person could just skip his meds and see how bad it gets?

ok should i move this to its own thread?

i was explaining to laura just how poorly the treatment pipelines perform and the fact that not one patient was asked to testify. patients could perforn better in that capacity if they are also trained to be clinical triial advocates.

The fierce urgency of now quote that Bryn used is also the first thing you read in our book. That quote is from Martin Luther King and it fits like a glove. Let's start stressing that we want patients at any pd policy planning, clinical trial planning , or process reviews tables as well as on IRBS. We want it now! Our goal should be to cancel the world pd congress in Montreal in 3 years due to lack of Parkinson's disease.


and imark thanks for the tip about budipine. is it available in Canada?

Here's a link to one happy customer about duodopa if interested.
http://neurotalk.psychcentral.com/sh...945#post701945

Paula,

I've been watching this over a year now as it is the most viable alternative to DBS once oral meds have run their due course. I asked my doctor about the hold up and why it was necessary to run essentially two trials...hmmm...last I checked Euros do not have a different set up for their gut than we do here. Then I hear there are problems with the pump here; my question is why does the pump have to vary from the Euro design? The real answer: someone wants to tweak an "American version" by changing the tubing or something in order to corner a patent or otherwise profit. My doctor pointed out numerous other treatments including many off-label available around the globe but not here without FDA interference. Don't these redundant tests waste millions in tax dollars and cause unneeded delay in getting treatment to us border on the unethical? I understand needing controls and standards, but when a therapy is now undergoing longitudinal studies in other countries, isn't that showing how ludicrously pointless the trials here are?

Is it any wonder why MS patients have formed their own clinical trials? I wish we could get more info on how they started doing this. If we could get funding and the right people involved it, we could actually make a difference in some lives.

I have watched a few videos on using the pump and it really just seems to take a few minutes. It beats waking up with a severely dystonic foot and having to hobble around for 30 minutes for meds to kick in. The pump is designed to give you a bit of a dopamine surge first thing so you kick on that much quicker. I also read that some patients actually require less of the medicine than they do with oral thanks to the steady plasma levels provided by the the pump. Just the relief of not having to time your life around meds wearing off is worth it to me. We could always start a line of fashionable pump bags...

Anyway, here is a good video from the EPDA web site (scroll all the way down).

As for the knowing that you are placebo, it is masked somehow. I thought I read that you still take your oral meds. So people with treatment benefit would lower their oral meds and people with placebo wouldn't know any better. They would still have a pump but it would be filled with something inert. That is the way I understand it but could be wrong.

Why don't you copy/paste your questions and start a new thread under clinical trials? Just a thought...

Laura