8/7/24
Ropinirole/Selegiline
For those of you who’ve been following my blog, you know that I’ve been trying Neupro, (rotigotine), delivered via a transdermal patch, for the last couple of weeks. It’s a little early to say, but as far as I can tell, there has been no significant improvement in my bradykinesia (slow movement) – 0r for that matter, any other negative symptoms associated with Parkinson’s. I haven’t yet got to the highest dose – that will happen next week– but if the lack of progress continues, the next step as recommended by my neurologist,will be to slowly go off of the patch and transition to ropinirole, another dopamine agonist.
Ropinirole is taken by mouth, 1 mg three times a day for the first week increasing to 3 mg three times a day by week three. I am not holding out much hope. Ropinirole is an agonist and so far my success rate with that class of medication has been poor.
Anticipating a lack of progress with ropinirole, I’ve started looking into alternative therapies. These fall into three categories:
First, other drugs that work by different mechanisms than than the agonists I’ve mentioned above. Selegiline, for example, inhibits a specific enzyme that breaks down dopamine in the brain, thus increasing its concentration. Rasagiline is a related drug that acts in a similar manner.
A second potential strategy dispenses with medication and instead requires direct manipulation of parts of the brain. For example, deep brain stimulation, a process requiring implanting an electrode in the part of the brain that controls movement, is a procedure that has been widely used in cases where other approaches have failed. The electrode is controlled by a pacemaker-like device, or neurostimulator, that is implanted under the skin in the upper chest. I’ll discuss this and another procedure, called focused ultrasound, in a forthcoming blog.
A third possible treatment is experimental and not yet available to the general public: the transplanting of dopamine-producing stem cells into the brain. These are intended to make up for the loss of neurons caused by Parkinson’s disease. They offer the possibility of a cure, unlike the other remedies listed above that only address of the symptoms of the disease. I’ll leave the discussion of stem cell treatments for another day.
Selegiline
As you know, dopamine is synthesized from L-DOPA. In turn, dopamine acts either as a neurotransmitter or a neuromodulator in the brain. Lack of dopamine, of course, is responsible for the symptoms of Parkinson’s disease. Too much dopamine can also be a problem.To prevent the accumulation of an excessive of dopamine, dopamine is broken down into inactive metabolites by a set of several enzymes acting in sequence beginning with the enzyme monoamine oxidase. In the end, the main end-product of these steps is homovanillic acid, which has no known biological activity and is eliminated in the urine.
Selegiline is a small molecule that binds to monoamine oxidase and prevents it from carrying out its function. The result is an increase in the amount of dopamine in the brain. What are the advantages and disadvantages of taking this drug? (From https://davisphinneyfoundation.org/selegiline-for-parkinsons-symptom-management/)
Advantages
1. It may show fewer side effects than dopamine agonists
2. It may help curb, depression, or anxiety
MAO inhibitors have a long history of use as a treatment for depression, and there is some evidence that–even at doses approved for use in Parkinson’s–selegiline may still affect depression.
3. It may help with gate dysfunction
4. May decrease daytime sleepiness
5. It is possible that the medication may have a neuroprotective effect, although that has not been shown definitively
Disadvantages
1. In clinical trials for selegiline, the most common side effects included nausea, lightheadedness, and abdominal pain.
2. Selegiline is broken down into amphetamine and desmethylselegiline, two substances that can cause adverse events including headache, insomnia, and irritability.
My intention is to speak with my neurologist and discuss whether taking selegiline is something to be considered, especially in view of the fact that the medications I’ve been taking have been ineffective. I have an appointment with her in a few weeks.