Parkinson's Disease Tulip


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Old 04-24-2018, 03:23 PM #1
eds195 eds195 is offline
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Default Gocovri Improves Dyskinesia in Parkinson’s Patients Over Long Term, Phase 3 Trial

Gocovri Improves Dyskinesia in Parkinson’s Patients Over Long Term, Phase 3 Trial Shows

Parkinson's Therapy Gocovri Improves Dyskinesia, Phase 3 Results Show
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johnt (04-28-2018)

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Old 04-28-2018, 02:26 AM #2
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There has been some discussion of Gocovri on the Parkinson's Movement forum, from which I've copied my contribution here:

The big question which remains to be answered is: Is Gocovri a straight dopamine replacement play or are some other factors involved?

Gocovri is an extended release version of amantadine. Amantadine is thought to be a minor dopamine agonist. Its advantage is that it has a long half-life, about 14 hours (as compared to 1.5 hours for levodopa/carbidopa).

According to Wikipedia [1]:

"Amantadine is a weak antagonist of the NMDA-type glutamate receptor, increases dopamine release, and blocks dopamine reuptake. ... Amantadine probably does not inhibit MAO enzyme. ... Moreover, the mechanism of its antiparkinsonian effect is poorly understood. ... The drug has many effects in the brain, including release of dopamine and norepinephrine from nerve endings. It appears to be a weak NMDA receptor antagonist ... as well as an anticholinergic, specifically a nicotinic alpha-7 antagonist like the similar pharmaceutical memantine."

Gocovri is being marketed as a treatment for dyskinesia. I suspect that its efficacy is mainly due to the longer half-life giving a more stable effect. This reduction in spikeyness means that plasma levels stay below the threshold for levodopa induced dyskinesia (LID).

If I am correct, you could get a similar effect using existing drugs by carefully timing your doses. In particular, increasing the frequency but reducing the size of your doses.

You can model minute by minute variations in the plasma levels of your drugs using:

Parkinson's Disease Measurement: PwP, surveys, trials, analysis

Ahlskog offers this advice regarding dyskinesia [2]:

"Just as too little brain dopamine translates into motor slowness, too much dopamine results in excessive movements, ie, dyskinesias.

Because dyskinesias represent an excessive response to dopamine replenishment, they can be abolished by reducing the individual doses of carbidopa/levodopa. ...

Unfortunately, reduction of levodopa to abolish dyskinesias may result in reemergence of parkinsonism. Some patients have a narrow therapeutic window between necessary and excessive levodopa effects. For such patients, the old drug amantadine works well to attenuate dyskinesias. If levodopa adjustments cannot control dyskinesias without inducing unacceptable parkinsonism, then the addition of 100 mg of amantadine twice daily is worth considering."

Sharma et al. are more specific [3]:

"Management of peak-dose dyskinesia involves adjustment of levodopa to a smaller and/or more frequent dose and/or reduction or discontinuation of dopamine-enhancing medications, such as MAO-B or COMT inhibitors."

References:

[1] Amantadine - Wikipedia

[2] "Cheaper, Simpler, and Better: Tips for Treating Seniors With Parkinson Disease"
J. Eric Ahlskog
Mayo Clin Proc, Dec 2011
Cheaper, Simpler, and Better: Tips for Treating Seniors With Parkinson Disease

[3] "Amantadine extended-release capsules for levodopa-induced dyskinesia in patients with Parkinson's disease"
Sharma VD, Lyons KE, Pahwa R
Therapeutics and clinical risk management, April 2018
[Full text] Amantadine extended-release capsules for levodopa-induced dyskinesia i | TCRM

John
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Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
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Old 04-28-2018, 05:19 AM #3
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Default Thanks for this John.....

I have been using Amatadine 100 twice daily for around 4 years and it has always done the trick for me. I know another PWP who has taken it for 9 years and it is still working just fine.

All in all one of the better drugs being hoofed on the market (with thanks to Alan Partridge).

Take care,
Neil.
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