[reverett123]

I have long heard that antihistamines were a PD "gold standard" in the years before the present "gold standard" of levodopa came along. Antihistamines were abandoned, not because they didn't help but because everyone went chasing the newest pretty face. That still leaves clues to be gathered about histamine. Consider the study below. Something seems to cause a doubling (yes, a doubling) of histamine in the specific regions of the brain that PWP become interested in. And they really looked at human brains and had controls for comparison as well! Pretty good work.

What really intrigues me and of which I am still too ignorant (but give me time ) is the part about the lack of metabolites. Does this mean that the histamine just collects there? If so, what does that do to the adjoining neurons? Inquiring minds want to know.....



1. J Neurochem. 2002 Jun;81(5):954-60.

Increased brain histamine levels in Parkinson's disease but not in multiple
system atrophy.

Rinne JO, Anichtchik OV, Eriksson KS, Kaslin J, Tuomisto L, Kalimo H, Röyttä M,
Panula P.

Department of Neurology and Turku PET Centre, University of Turku and Turku
University Hospital, Turku, Finland. juha.rinne@pet.tyks.fi

We investigated histamine concentration in post-mortem brain samples of patients
with Parkinson's disease (PD, n = 24), multiple system atrophy (MSA, n = 8) and
age-matched controls (n = 27). Histamine concentrations were significantly
increased in the putamen (to 159% of the control mean), substantia nigra pars
compacta (to 201%), internal globus pallidus (to 234%) and external globus
pallidus (to 200%), i.e. in areas which play a crucial role in the motor
behaviour and which show typical functional alterations in PD. In MSA no
significant differences were seen. Tele-methylhistamine (histamine metabolite)
concentrations were unchanged in PD. These results indicate that histamine
concentration, but not its metabolism is increased in PD, but not in MSA. This
finding may have implications in developing new drug therapies for PD and in
differential diagnosis between PD and MSA.

PMID: 12065607 [PubMed - indexed for MEDLINE]

[lurkingforacure]

I remember long ago we took Benadryl once for something and the PD pretty much flat-out disappeared for hours, it was both scary and amazing. We read the bottle and realized you shouldn't take it with drugs like Azilect, so couldn't do it again. But I've often wondered how it was that Benadryl had such a wondrous effect. Found this from webmd:

This medication works by blocking a certain natural substance (histamine) that your body makes during an allergic reaction. Its drying effects on such symptoms as watery eyes and runny nose are caused by blocking another natural substance made by your body (acetylcholine).

So it may have helped us feel better because it was blocking some histamine production....and/or by blocking acetylcholine, which might have the effect of normalizing the dopamine/acetylcholine ration which is otherwise out of whack because of the PD.

[mrsD]

Histamine is a neurotransmitter in the brain.

It is a trigger for the release of other specific neurotransmitters.http://www.landesbioscience.com/curie/chapter/4436/

http://www.unboundmedicine.com/medli...physiology%5D_

The only antihistamines that cross the BBB are the first generation ones. (typically they cause drowsiness).

Claritin, Allegra, and other non-drowsy types typically do not.

Benadryl (diphenhydramine) has long been used in certain movement disorders.
http://www.minddisorders.com/Del-Fi/...hydramine.html

[mudfud27]

Histamine is an interesting neurochemical, partly because it is widely distributed mostly via projections from the tuberomammilary nucleus to almost everywhere in the brain. This extremely widespread innervation means both that it must be important in some way but also that it isn't very specific. This has made it hard to study.

There is some evidence that there is a specific histamine transporter in neurons and glia but to the best of my recollection (I haven't looked into this since about 2008), the molecular machinery hasn't been identified yet. The lack of histamine metabolites in PD brain despite increased levels of histamine may suggest there is a defect in the cell type responsible for metabolism or that it is just metabolized remotely (taken up into the surrounding capillaries).

The original poster is correct that antihistamines (although much more often anticholinergics) were some of the original PD medications. Antihistamines can work because there are extensive histaminergic projections to the substantia nigra pars reticulata. Dopaminergic neurons in these structures are known to be inhibited (indirectly) by histamine, so blocking it can enhance dopamine signaling.

Antihistamines were not abandoned because doctors went "chasing the pretty face" of course; they were abandoned because levodopa is VASTLY more effective and has VASTLY fewer side effects than antihistamines in treating PD. After all, it is the lack of dopamine-dependent neuronal signaling that directly produces most of the motoric effects of PD.

[mudfud27]

Originally Posted by lurkingforacure

I remember long ago we took Benadryl once for something and the PD pretty much flat-out disappeared for hours, it was both scary and amazing. We read the bottle and realized you shouldn't take it with drugs like Azilect, so couldn't do it again. .

What made you think you should not take benadryl and rasagiline together? I have plenty of patients who do so without particular difficulty, unless you're referring to some increased drowsiness.

[Aunt Bean]

This is crazy, but my dad has been having more balance issues lately...still have not found anything besides benedryl that will help him get a better nites sleep. This week he took it 2 consecutive nites and his coordination was so much better the next day...was this from sleeping or from the histamine reaction / or both. I didn't notice him stagger once yesterday(and he was so close to falling / so many times the day before)???????
Our diet did not change (except we did have talapia fish 2 days in a row) YUM-yum.

[johnt]

mudfud27,

In your experience does the use of Benadryl in addition to the standard anti-Parkinson's set of drugs (rasagiline, agonists, levodopa etc.) offer any marginal advantage?

I do hope you continue to post on this forum. There is much that we can learn from you. Equally, there is much that you can learn from us who live Parkinson's 24/7.

John

[mudfud27]

Originally Posted by johnt

mudfud27,

In your experience does the use of Benadryl in addition to the standard anti-Parkinson's set of drugs (rasagiline, agonists, levodopa etc.) offer any marginal advantage?

I do hope you continue to post on this forum. There is much that we can learn from you. Equally, there is much that you can learn from us who live Parkinson's 24/7.

John

Hi, John-
First: anything I say here is a generality, not meant to provide specific medical advice for you or any individual.

That said, I will say that I have not often seen Benadryl be useful as an adjunct for bradykinesia or rigidity. It is sometimes helpful for tremor. For some reason I don't understand, though, patients seem to habituate to it rapidly and the benefits only last a short time. And as you probably know, it causes a lot of drowsiness. So I've seen some people who get a short term benefit from using it every so often when they have a social function, etc. but not any kind of long term or even frequent solution, for the most part.

Thank you for your kind words, I agree there would be much to learn from patients here and it would be nice to share some of what I know. *edit*

Take care.

[Arsippe]

Mudfud, my experience w/Benadryl is consistent with your description of its efficacy. Initially, as an experiment, I took one 25 mg at the start of the day and noticed a moderate to marked improvement in my hand tremor. After a couple of days, I felt I needed to add another 25mg about four hours later at noon. This went on for a few more days, but I began to notice less improvement and more tremor, maybe even more tremor than I had before I started w/the Benadryl. The experiment lasted about two and a half weeks and then I stopped taking the Benadryl. I am now occasionally taking an Ibuprofen PM pill, which is 220 mg ibuprofen w/a 38 mg component of Benadryl. This does seem to be helping just a bit--more than the Benadryl alone did. I only take it when there is some kind of challenge coming up. I will have to say that there is nothing I've taken and nothing I've done that really is efficacious for my tremor other than the recumbent bike doing 80 rpm for 40 minutes. Just to complete the picture, I am tremor dominant, have a one year old PD diagnosis, take no meds (other than the above), and have been having PD symptoms probably for years, unrecognized, both motor and non-motor.