amantadine, norepinephrine, locus coeruleus, methylphenidate (Ritalin), ceruleus

[aspergerian]

In 2012 I was taking 3 25/100 of c/l per day and was developing

tiredness. A neurologist suggested adding amantadine 2 per day of 100 mg.

Within hours of taking the first amantadine, my walking had improved

dramatically. I noticed and several neighbors noticed. At least one

HU thread mentions the LC (locus ceruleus) in regard to

norepinephrine. The HU search function identifies no such comment,

suggesting the titles are searched but not comments' text. At least

one comment mentions the important finding that amantadine helped

many individuals with PD. Here's some background (also mentioned

elsewhere) and "recent" findings.

Background:

"The history of amantadine is of interest because of its

serendipitous discovery as an anti-Parkinsonian agent. Developed as

an antiviral agent, it was used widely in nursing home populations,

and Schwab noted its unexpected benefit on tremor, balance, and

akinesia in both Parkinson's disease and postencephalitic

parkinsonian patients (Schwab et al. 1969)."

Quote from ncbi.nlm.nih.gov/pmc/articl...

Amantadine in the treatment of Parkinson's disease.

Schwab RS, England AC Jr, Poskanzer DC, Young RR.

JAMA. 1969 May

19;208(7):1168-70.

ncbi.nlm.nih.gov/pubmed/581...

Recent findings:

1. Neuronal loss is greater in the locus coeruleus than nucleus

basalis and substantia nigra in Alzheimer and Parkinson diseases.

Zarow C, Lyness SA, Mortimer JA, Chui HC.

Arch Neurol.

2003 Mar;60(3):337-41.

[LC aka locus ceruleus]

jamanetwork.com/journals/ja...

2. The noradrenaline transporter as site of action for the

anti-Parkinson drug amantadine.

Sommerauer C, Rebernik P, Reither H, Nanoff C, Pifl C.

Neuropharmacology.

2012 Mar;62(4):1708-16.

ncbi.nlm.nih.gov/pubmed/221...

3. Clinically relevant doses of methylphenidate significantly occupy

norepinephrine transporters in humans in vivo.

Hannestad J, Gallezot JD, Planeta-Wilson B, Lin SF, Williams WA, van

Dyck CH, Malison RT, Carson RE, Ding YS.

Biol Psychiatry.

2010 Nov 1;68(9):854-60.

ncbi.nlm.nih.gov/pmc/articl...

Cites 1 and 2 are very important and are often ignored in studies

about PD and dopamine. When I first took c/l, I noticed a big

improvement. The next big improvement occurred when amantadine was

added to my daily regimen. More recently, adding 5 mg/day of

methylphenidate has helped ease daily tiredness.

Nonetheless, Parkinson's deterioration continues in its unhurried

pace. Amantadine efficacy seems to slowly decline, and I do not

know how long the methylphenidate will continue to be helpful.

[Hikoi]

Amantadine is popular in some countries. Good for tremor. Havent heard or read whether it is good for drowsiness. It is known to give hallucinations for some people.

[aspergerian in reply to Hikoi]

Soon after my first amantadine was so helpful, I found Savery F 1977 and received a copy of the very informative article.

Amantadine and a fixed combination of levodopa and carbidopa in the treatment of Parkinson's disease.

Savery F.

Dis Nerv Syst. 1977 Aug;38(8):605-8.

ncbi.nlm.nih.gov/pubmed/328244

Forty-two patients with Parkinson's disease were given amantadine HC1

(Symmetrel) and placebo in an 18 week double-blind cross-over study to

determine if amantadine provided additional benefit when combined with

levodopa and carbidopa (Sinemet). Analysis of our results showed that

amantadine effected a 92% improvement over baseline in symptom scores

and a 95% improvement over baseline in activity impairment scores,

compared with corresponding values of 4% and 18% for placebo. The

difference between amantadine and placebo was statistically significant.

Except for one case of mild livedo reticularis and two of blurred

vision in the amantadine group, side effects were generally similar for

amantadine and placebo in type and frequency. This study provides new

evidence of the importance of combinations of antiparkinson drugs to

achieve maximum therapeutic benefit.

Zarow et al 2003 brought attention to norepinephrine in PD, having reported damage to the locus coeruleus ncbi.nlm.nih.gov/pubmed/126...

Sommerauer et al 2012 found "The noradrenaline transporter as site of action for the anti-Parkinson drug amantadine" ncbi.nlm.nih.gov/pubmed/221...

Dyk et al 2010 reported that "Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo" ncbi.nlm.nih.gov/pubmed/206...

My responses to L-dopa, amantadine, and methylphenidate suggest that my PD involves deterioration of the substantia nigra and of the locus coeruleus.

[shadesofnothing in reply to Hikoi]

Yes, it caused me horrific hallucinations - there were moments when I got so bad, I very nearly got dragged off to the funny farm.

I'm still on, but half the dose, been ok for years now, :).