Science Tuesday: Sublingual Carbidopa/Levodopa

“The human brain doesn’t come with an instruction manual.” Bill Engvall

“The great events of the world take place in the brain.” Oscar Wilde

Levodopa: Levodopa markedly improves motor symptoms for the majority of people with Parkinson’s. The pharmacological effectiveness of levodopa is quite good; however, it has less efficiency in controlling the non-motor symptoms.

When mixed with the enzyme inhibitor carbidopa, which prevents the breakdown of levodopa in the periphery, levodopa can better navigate the circulatory system. Levodopa can then pass through the blood-brain barrier and get to the brain, where the levodopa is modified to become dopamine. Thus, carbidopa/levodopa is a big help for many people with Parkinson’s. The goal here is not to discuss the limitations of carbidopa/levodopa, except to mention it has a half-life of ~45 mins, which means one can have on/off periods that come and go as one is constantly taking this drug.

“Follow your heart but take your brain with you.” Alfred Adler

Definition of Sublingual and How it Works: Sublingual means underneath the tongue. For example, a sublingual medication is a pill/tablet/lozenge that dissolves under the tongue. Administration through direct absorption into the mouth provides an advantage to medications you swallow since they go directly into your bloodstream and do not go through your digestive tract before being absorbed into the bloodstream. When a chemical comes in contact with the mucous membrane beneath the tongue, it is absorbed. The sublingual glands get their primary blood supply from the sublingual and submental arteries, which are branches of the lingual artery and facial artery; both of which are branches of the external carotid artery.

Sublingual administration has certain advantages over oral administration. Being more direct, it is usually taken up faster, and the substance will be susceptible to degradation/destruction only by salivary enzymes before entering the bloodstream. By contrast, orally administered drugs must survive passage through the more hostile (but physiologically necessary) environment of the digestive system, which risks degrading drugs/compounds, by either stomach acid or bile, or by many different enzymes.

“The human brain, then, is the most complicated organization of matter that we know.” Isaac Asimov

Sublingual Carbidopa/Levodopa (*please see medical disclaimer statement at the bottom): After I stopped using the dopamine agonist, Ropinirole, I found these on/off periods were real and a nuisance at certain times.

Moreover, I thought to myself, why couldn’t I stick a half-tablet of carbidopa/levodopa under my tongue and see what happens. So I tried it [I take twelve tablets of 25 mg/100 mg carbidopa/levodopa per day (taking 2.5 tablets four times/day at 4 hour intervals, and two tablets at bedtime)]. My Neurologist applauded that I used a pill cutter to cut my tablets in half to gain better control of my daily therapy.

The idea was simple, would the half-pill get to my brain faster than the two tablets taken the usual route by swallowing them? To my surprise, it really did work. This can usually take 30-45 minutes, and it can vary depending on is there protein in your gut competing for the amino acid transporter system, and so forth. Remember that levodopa is an amino acid-type molecule, which is taken up by amino acid transport system in the GI tract and the blood brain barrier. Also remember that protein is made up of amino acids; thus, competition between amino acids and levodopa for the same type of uptake receptors..

Sublingual carbidopa/levodopa bypasses the gastrointestinal system and gets into your bloodstream rapidly, I would say in 12-15 mins you are feeling the effect of the levodopa.

I talked to my Neurologist about this process and my use of taking one-half of a carbidopa/levodopa tablet sublingual. Here are some additional comments:

  • My Neurologist agreed that it worked the way I described it above, but then he asked about how it tasted? My response was, “It tasted OK, neither good nor terribly bad.”
  • I also qualified when I would use this method of taking carbidopa/levodopa, these scenarios. First, during a very stressful situation where I could feel my body consuming dopamine faster than usual. Second, during exercise endeavors where I could also feel the dopamine consumption process being accelerated. Third, when the occasional on/off period was a real nuisance and it was happening faster than usual;
  • I would not use more than one-half of a tablet of carbidopa/levodopa.
  • How often have I done sublingual carbidopa/levodopa? Perhaps six-eight times in the past four weeks. Not often, but it does take some practice to perform.
  • I checked around the internet and found several folks at HealthUnlocked (the Parkinson’s disease site) have commented about using carbidopa/levodopa under their tongue.

“The chief function of the body is to carry the brain around.” Thomas A. Edison

Proper Steps to Taking Sublingual Drugs (taken from the Compounding Pharmacy of America):

1. Drink water before administration.
Drink plenty of water 10 to 15 minutes before placing a sublingual tablet. This step ensures you produce an adequate amount of saliva necessary to dissolve the tablet

2. Place the tablet in the correct area of your mouth.
For sublingual administration, place the tablet under your tongue and wait until it dissolves. For buccal administration, place the tablet between your cheek and your gums.

3. Avoid washing away the medication.
After the tablet has dissolved, avoid eating or drinking for at least 30 to 45 minutes. Food and liquid can wash away a portion of your dose and result in weakened effects or the return of your symptoms.

4. Avoid interfering with absorption.
Do not brush your teeth immediately before or after you place your medication. Also, do not smoke or use chewing tobacco for two hours before and after taking your medication. Both activities can prevent the mucous membranes in your mouth from properly absorbing the medication.

Closing Comments About Sublingual Carbidopa/Levodopa: Using the sublingual approach to occasionally take carbidopa/levodopa definitely worked.

There is an interesting case study using sublingual carbidopa/levodopa in two Parkinson’s patients, which further indicates the utility of taking carbidopa/levodopa under the tongue to more rapidly deliver the drug to the brain: Bhirud PH, Kate JA. Perioperative sublingual levodopa in Parkisnon’s Disease: A useful alternative! Indian J Anaesth. 2017 May;61(5):432-434. doi: 10.4103/ija.IJA_178_17. PMID: 28584355; PMCID: PMC5444224 (Click here to download the paper).

And in another paper, Gupta HV, Lyons KE, Pahwa R. Old Drugs, New Delivery Systems in Parkinson’s Disease. Drugs Aging. 2019 Sep;36(9):807-821. doi: 10.1007/s40266-019-00682-9. PMID: 3116158 (Click here for article), the authors provide up-to-date information about infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodopa, intrajejunal infusion of levodopa, and sublingual apomorphine.

*Medical Disclaimer: Remember that I am a protein chemist NOT a physician; therefore, do not consider this as medical advice. Please consult with your Neurologist before trying subligual anything, but especially carbidopa/levodopa (i.e., Sinemet) because in my thinking it could also accelerate the bad effects of carbidopa/levodopa (e.g., orthostatic hypotension, dizziness, headache). Please be careful if you are thinking about trying sublingual carbidopa/levodopa.

“There are billions of neurons in our brains, but what are neurons? Just cells. The brain has no knowledge until connections are made between neurons. All that we know, all that we are, comes from the way our neurons are connected.” Tim Berners-Lee

Also see these blog posts:
Treating Parkinson’s with a Dopamine Agonist: The Ropinirole Taper
Treating Parkinson’s with Carbidopa/Levodopa
Purple Haze of Parkinson’s: How Dopamine Works

Cover Image by Gerd Altmann from Pixabay

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