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Parkinson's Movement
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Benadryl (diphenhydramine) and Sinemet interaction

Awhile ago I listed the things I take and how when I stopped benadryl for awhile I could sure tell the difference in a bad way. Then I restarted the 1/2 doses of benadryl. Sinemet works so much better with a little bit (half a tab) of Benadryl. However, I was just using the drug interaction tool at medscape and for the 1st time I input benadryl...whoops! Come to find out that my little half a dose of benadryl is known to increase the efficacy of levadopa, BUT it raises the risk of TARDIVE DYSKINESIA!!! Just in case anyone else is taking benadryl and didn't already know that risk is why I am posting this. I am going to try again to quit the benadryl, just because TD is my worst fear, next to a spider crawling across my arm.

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Hmm. I did a Google scholar search on levodopa, benadyl, and tardive dyskinesia and was unable to confirm this. Here is a good reference: books.google.com/books?hl=e...

Tardive dyskinesias are adverse effects caused by anti-psychotics. The reference lists benadryl as something that counteracts tardive dykinesias.

I used to respect Medscape but have found a number of erroneous items there. Even if something posted there is written by a doctor and is seemingly authoritative and thoroughly referenced, I have found it ain't necessarily so.

Not sure that Medscape is wrong on this, but it does need to be confirmed.


According to this link benadryl "blocks the action of acetylcholine (eg an anticholinergic effect)." Anticholinergics, like amantadine, are usually used for the on/off condition.



Tardive Dyskinesia Mt. Sinai Hospital:



Some medications may help decrease symptoms, such as:







Antiseizure drugs

Antipsychotic drugs that may help with movement disorders


+++++ Diphenhydramine +++++

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Thank u for always providing excellent information and links! Could u speak to this: Confusion and disorientation after beginning carbodopa/levodopa as well as when the dose changes either up or down? Thank you

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I think the confusion and disorientation are side effects of C/L. Here is a complete list of side effects including.

"..confusion, hallucinations, anxiety, agitation, depressed mood, thoughts of suicide or hurting yourself;"


PWP have decreased dopamine levels (if any at all) and are in essence 'flat-lining' and when dopamine (from sinemet) is added it peaks like a heart EKG and with added doses (throughout the day) a pattern of ups and downs occurs. With the alteration of dopamine levels from sinemet, the size of the peak may be raised or lowered, depending on dose. Dopamine is the neurotransmitter which effects balance, mood, emotional response, the ability to experience pleasure or pain and by changing the quantity of dopamine you are in affect reacting like a junky to a different dose of a drug. In many ways the fluctuations experienced by PWP (on levodopa) are very much like those of junkies - whether we want to admit it or not.

We are all junkies awaiting the next dose.

Hence the advent of Rytary, an attempt to have a continuous (level) response and to eliminate the peaks and valleys.

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Thank you! Very good info on the site you sent .The neurologist is having us try 1 tablet for 4 days then nothing for two weeks to see if symptoms change.


Yes others are posted, Tardive dyskinesias are usually caused by neuroleptic drugs that block dopamine as part of their mechanism of action. Diphenhydramine is an anticholinergic so I'm not sure that this information is correct.

That having been said, some of the side effects of anticholinergic medications can be negative In their own right (sleepiness, cognitive changes, balance issue etc.).

If something is working for you, that's good but this really feels like a question for your doctor or your nurse specialist


Yes, JD, a good question for the physician.. My new neuro has advised me to stop using diphenhydramine among other things. I was given a list to avoid while he tries me out on Azilect.

Off topic---I was moving a sprinkler hose and it was covered with fire ants. I did not notice them until I had carried the hose a few feet and their feet had carried them all over my fingers, back of my hand and over my wrist where they simultaneously punished me for disturbing their drinking. Afterward, I noticed I had regained tactile ability in that right hand to the point I have not known for a few years. Sadly that renewal of function lasted a mere 3 hours or so. It was real nice to enjoy two fully functional hands. Too bad it takes ant bites.


Holy Toledo, what a jarring turn of events!


Guess what? I did it again, on purpose this time. It worked again. The bites I received today really were not all that painful, probably because I was expecting it this time. I was out in a field when I saw this mound, a fire ant mound, they make mounds after a rain. So I decided immediately to do an experiment. I tell anybody who thinks I am a nut, "If you suffer PD you try anything that might decrease your impairment." The result was the same as the first time, improved walking gait and tactile ability improvement in my affected hand. Silvestro, if you read this, I researched the product made by that German pharma, Lundbeck (?) and find they no longer list Parkinsan among the line of medicines they market. I don't know if any other pharma will make it, Lundbeck probably has a patent. This is very very dispiriting for me and all of us since the active chemical (budipine hydrochloride) was promising as a neuro regenerative therapy for both MS and PD patients. Oh well Texas is not about to run out of fire ants in my life time. :(


I would contact the company to see if the drug exists and is available for prescription. Tell them your story about the fire ants which led you to discover budipine. If it exists, even if it not listed as a PD medicine, it can be prescribed for 'off label use'. Also tell your doctor this story and get him/her to write a prescription.

I admire your determination to get at the truth and it reflects an objective mind. I understand your frustration but keep trying to obtain the drug. In the studies I read I wonder why budipine did not go worldwide. It certainly looks like an advance in PD drug therapy.


Yes, I am definitely going to mention budipine and how I learned about it at my next appt with the movement specialist I just started seeing earlier this month. I hope he doesn't fall off the chair laughing. He doesn't strike me as a humorless man, a large (fat) neuro of Russian Jewish ancestry with a big, successful practice. He should be a happy fellow. I hope he knows of Parkinsan already. Just so I don't get kicked out; It'd be hurtful if he took it that I was joking or in any other wrong way. I'll see him again October the fourth.


Bring in the budapine studies and its chemical similarities to fire ant venom. FA venom is 99% piperidine and the chemical formula for budipine is 1-alkyl-4,4-diphenyl piperidine.

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Meghan at Lundbeck pharma here in the US at their Illinois ofc. told me that Parkinsan is a Lundbeck product, however it has not been approved for sale in the US. BTW I think Azilect is also a Lundbeck product.

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Nope, I made a mistake Azilect is an Israeli co. product, Teva pharma


Well that's typical. The costs, tests, etc...to get a drug approved are are stiffer here in the US than in Europe. Well, we know the basic chemistry of a drug that can help you and now is it possible to find something similar in structure and effect? Just a thought.


Well you cannot use pure piperidine. It was tested with levodopa in 1977 and found to antagonize its effect:

Antagonism by piperidine of levodopa effects in Parkinson disease.


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I am trying to decide if it is safe to order from a China based, probable patent stealing counterfeiter of Budipine. My PD afflicted man says, "You've got PD give it a go." My good man side says no on ethical and cautious grounds, you do not know what you will get, you aren't equipped to test it. I let two fire ants bite me this afternoon. Antagonistic or not I am experiencing better use of my right hand. I can open the Perrier bottle now with my right hand and you probably know how tough those little suckers can be. If you don't have a good grip forget it.

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It sounds like a risk/return dilemma. I looked at the chemical formula they posted on the webpage and yes it is Budipine. I guess it depends on if you want to take the chance by taking a small dose and see what happens. If you contact the Chinese company (and they want rationale), tell them you are conducting a PD study comparing the effect of Solenopsin A, fire ant venom, a natural piperidine product, versus Budipine, a synthetic piperidine product in a small study.

Are you on an anticholinergic at the moment? I have been looking into the properties of Budipine and here is an interesting study:

Effects of the antiparkinsonian drug budipine on neurotransmitter release in central nervous system tissue in vitro.

"It is concluded that both anticholinergic and indirect dopaminomimetic properties contribute to the antiparkinsonian effects of budipine, whereas biperiden exhibits mainly anticholinergic effects."


This is a German study and both budipine and biperiden are of German origination.

Biperiden is listed as an 'essential 100 drugs' by the WHO and is easy to purchase (without a prescription):




thanks for helping.


BUZZ1397 and silvestrov

I just heard something on the news this morning that bee stings have been found to help Parkinson's. It reminded me of your fire ant theory. It didn't go into a lot of detail so I googled it and MJF did a trial which seemed to be positive, but looks like it was done in 2008. I've attached the study. Do you have any idea why they wouldn't have pursued this sooner and/or have you heard of this before? I don't think getting stung by honey bees sounds like the ideal therapy, but if it stops the progression it might be worth it??


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As coincidence happens, I was at the movement specialist this afternoon and mentioned it. They knew all about piperidine, fire ant venom and the Lundbeck product that isn't available for sale in the US. Didn't offer a explanation though as to why it isn't. I am determined to keep on seeking fire ant bites every 4-6 days. I wouldn't try bees though because their stingers are fairly large, much larger that tiny ant stingers. And bees are really hard to catch unless you know a bee keeper that wouold let you "use" their hive therapeutically. BTW I have found that about 5 ants biting my hand is a good "dose". Don't get the idea I am allowing myself to be covered up. Also of interest is I have stopped getting ant bite bumps afterward, as if my body has become adjusted to the piperidine



It causes me to be angry, that Lundbeck's Parkinsan nor the generic budipine are sold to Americans with movement disorders. Would I give a butt kicking to the a hole that blocks it, yep


Sorry to hear about the fire ants. Having lived in Georgia I have been stung by them and know it is not a lot of fun. What also occurred to me was to check out the chemical class of fire ant venom and see if it or a chemical derivative of it has been used to treat PD.

"Fire ant venom contains a chemical called piperidine."


Use of n-piperidine derivatives for the treatment of neurodegenerative pathologies

US 20070191427 A1


Clinical efficacy of budipine in Parkinson's disease.

"The lipophilic t-butyl analog of 1-alkyl-4,4-diphenyl piperidine, budipine, possesses a polyvalent spectrum of mechanisms of action."



The above study was done in Germany and so is the supplier of budipine.

Budipine Provides Additional Benefit in Patients With Parkinson Disease Receiving a Stable Optimum Dopaminergic Drug Regimen


The antiparkinsonian agent budipine is an N-methyl-D-aspartate antagonist



"Dexetimide (brand name Tremblex) is a piperidine anticholinergic. It is a muscarinic antagonist that is used to treat drug induced parkinsonism."


Dexetimide is an old drug which has been tested on 'male psychotic patients':



I do not think Tremblex is available anymore.


The question is is can you get your hands on budipine?


It would be easy just to allow fire ants to attack my hand a little bit again. Call me experiment prone. I'm certainly going to wait for these sore places on my and to go away. There seems to be some lingering improvement in tactile ability in that right hand since the ant bites. This serendipitous event inspired me to google venom and Parkinson's. I found several tings about venom being researched but nothing on ant bites. But you did. You have a way with search terms.


For whatever reason, I am glad to hear your hand has felt some improvement.

Fire ant venom is called solenopsin (a piperidine alkaloid) and it is listed as a possible therapeutic agent:

Compositions and methods relating to solenopsins and their uses in treating neurological disorders and enhancing cognitive and physical performance


In the above (boring) patent application the potential drug is targeted for Alzheimer's disease (and later mentions Parkinson's).

There is a related substance which is good for potentiating nutrients and has been shown to be neuroprotective in PD models: piperine.

Article title:

Anticonvulsant mechanisms of piperine, a piperidine alkaloid

Piperine in PD:

Neuroprotective effects of piperine on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model.


I use piperine and I take it with the largest dose of nutrients because it increases their bioavailability by (a minimum of) 30%.


In some cases piperine can massively increase the bioavailability of nutrients like curcumin:

Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.

"Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug ....the increase in bioavailability was 2000%."


Here is when the heavy warning comes in. I am not taking any drugs and piperine can increase the bioavailablity of drugs which will make them work at lower doses. So, say you are taking a dopamine agonist, piperine will make this drug work much more efficiently at and at lower doses. So the standard DA dose will now be a massive dose and all the side effects will be heightened. A dangerous drug made even more dangerous.

Piperine is also a MAO inhibitor.

Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid

from the pepper plant Piper nigrum, for possible use in Parkinson’s disease


So by taking piperine with Azilect it may make it work much more efficiently and cause problems. It is good to be cautious.

This is why I try to keep myself off of PD drugs because it limits therapeutic options.

Piperine is actually used with rifampicin, a front line TB antibiotic, and has been shown to lower the dose from 450 mg to 200 mg. The drug is called risorine:

I found it interesting that the videographers used the music from the soundtrack Inception. A strange surprise.

Finally, I researched the possible therapeutic options for fire ant venom because of my Lyme disease research. Your story, being stung by fire ants and felt symptomatic improvement, reminded me of this story:

Bee attack cures Lyme disease, saves woman’s life



What a coincidence (?) One of the ingredients of GABA-plex that I've benefited from taking it concomitant w/Sinemet is some extract from the Piper nigrum plant (5 mg Piper Nigrum fruit standardized to piperine 95%). Makes more and more sense that this capsule helps me. The GABA is kind of anti-depressant, I believe, and te Piper nigrum is enhancing the effect of levadopa, I believe. Am I following or way off track?


Piper nigrum is a great herb that does a bunch of things....including potentiation of other supplements and drugs (including levodopa). It is a great anti-inflammatory , antimicrobial.... GABA is an 'inhibitory' neurotransmitter and helps to calm the mind. The bad news is if you have a positive (calming) response to GABA it means you have a porous blood brain barrier. GABA dose not normally cross the blood brain barrier:


And this is why I am a proponent of using theanine. Theanine. It crosses the BBB and raises GABA (and other neurotransmitter) levels:


Taurine is an amino acid which also crosses the BBB and has a calming effect and has a significant relationship to PD:

Reduced plasma taurine level in Parkinson's disease: association with motor severity and levodopa treatment.


Getting back to piperine/Piper nigrum, if it has worked for you in your current mix of drugs/herbs...etc.. it is obviously safe for you and keep taking it. 5 mg is not a huge dose and 15 mg is recommended for 1 day (divided into 5 mg doses).


Oh, this GABA-plex product of Swanson's also has l-theanine and l-tyrosine and l-glycine. Must be something there that calms me. Say if I have a porous blood brain barrier does that explain my being open minded? :) Explain why sometimes I can filter out my wife's noises? Her words can just go in the right ear and out the other. Porous brain, little to no annoying retention.


I took a benadryl one night, thinking it would help me snooze through my Restless Leg. Instead, I floated in a daze through Restless Body all night. My neuro cautioned against taking it, saying benadryl has a number of ghastly side effects for us PwP and some for other people, too.

Oh btw, I just started on klonazepam -- we'll see if that makes a difference.


Beckey looks like Benadryl and Klonazepam could both potentially increase the risk of dementia from what I read here brightfocus.org/alzheimers/...

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You'll let us know won't you?


Oh no! They just started me on clonazepam for the restless leg. Oh well.

You know, I don't know why they call it restless leg. They should call it bullisome leg.

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Why not Ropinoral (Requip)?


Good question!


I take Benadryl Liquid Gel caps after an ER Dr. advised me that it would help control my Dystonia attacks to take a couple throughout the day with my Parkinson's meds. It has been one of the best things to help my "Dystonic storms" but surprisingly I have only met 2 Dr.'s that knew that Benadryl can be beneficial to ppl with PD.


I know and all they had to do was read about its use to enhance the effectiveness of the Rx meds. It's not like a secret. Still, the available reading on it also says that it increases the chances of getting tardive dyskenesia. That's different from your dystonia, isn't it? Hey I hoope the neuro lets me get back to using half caps of benadryl after I am established on the azilect and rytary regimen they want me to be on. Benadryl was also helping with my allergies, of course. Have a happy day.

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Yes Dystonia and Dyskenesia are different.

Tardive Dyskenesia causes stiff, jerky movements of your face and body that you can't control. You might blink your eyes, stick out your tongue, or wave your arms without meaning to do so.

Dystonia is a movement disorder in which a person's muscles contract uncontrollably. The contraction causes the affected body part to twist involuntarily, resulting in repetitive movements or abnormal postures. Dystonia can affect one muscle, a muscle group, or the entire body.

I have both Dystonia and Dyskenesia as a side effect from taking Carbidopa/Levadopa medications.

So i guess it comes down to your own personal choices. My advice is to talk to your Dr. and ask question and talk to others that have PD, and research, research, research, before making the decision you are most comfortable with.

I wish you all the best,


(and yes taking Benadryl increases your chances of getting Dementia)



Yes, I have read recent studies that the class known as Anticholinergics (it includes benadryl I guess) causes or increases chances of dementia. I would stay away from them. I've got 99 problems and I don't want that one.

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Me too, no more problems please. I can live w/o Benadryl, just don't want to live in a world w/o ice cream...or Fritos...or beer...or mexican food :)

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Haha, things we can't live without, I guess I would have to put my little dog on the list who I nicknamed "pee wee" (see the family resemblance).

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