Sunday, January 20, 2013

My Drug Buddy

Whether or not you're a neuroscientist, or have P or don't, you have probably heard of the oldest and most well known drug for P: L-DOPA. As the great Big Black sang: "L-DOPA fixed me, alright".

Now I don't share Albini's cynicism, but I must admit the drug has some unappealing properties, especially for someone my age. First of all, it stops working at some point. Actually that's an exaggeration, it's more like diminishing returns. It becomes less and less effective over some number of years, so that you need more to get the same effect. Eventually, I gather you start to need deep brain stimulation implants or some other surgery, but that's another post altogether. But while you're on the drug, you and your doc are riding a line between giving you what you need to be controlled, and trying to avoid triggering what is called "dyskinesia" which is a technical way to say unwanted movement. Have you ever seen MJ Fox on TV and how "he's all moving and shaking", as Rush Limbaugh famously mocked a few years ago. Now if he weren't such an uncharitable jackass, I might forgive Rush for his ignorance. He accused Fox of going off his meds to exaggerate the effects of the disease when testifying before Congress about stem cells. What the dolt didn't realize is that bobbing and weaving is the drugs. MJ probably juiced himself up pretty good actually because... you know... he's talking to Congress!

In any case, eventually this reaction to L-DOPA, or actually its modern equivalent Sinemet, gets triggered by the drug and then it doesn't go away. You will always have some of that when you take the drug. Sinemet evidently works great for a while (never taken it), but doctors like to save that one for later with someone like me who will probably be dealing with P for 40-50 more years (I hope).

So why does this happen you may ask? I should back up and explain why it works in the first place. Bear with me if you already know all this. PD, which is almost certainly the cause of my (P)arkinsonism (the difference and the reason for the hedge are again fodder for a future post), occurs when a small specific group of neurons that make a chemical called dopamine die off. Dopamine is important for a lot of things as we'll see, but it turns out that the dopamine from these specific cells is really important for movement coordination and initiation. This is not good but there's a silver lining: the dopamine that is still made by the remaining cells does a pretty decent job of filling in for the dead guys. So if you can get them to make more it helps. L-DOPA is a chemical that the remaining cells can use to make more dopamine. Eventually, presumably as more of the cells die, this works less well and you need to feed them more. That's when you start to kick off the effect of too much dopamine, which is dyskinesia. Basically, the effects become less stable than they used to be so it's hard to find a good level sweet spot.

Anyway, I've never taken Sinemet. Does this mean I am saving it up for when it will count, or does it mean I am wasting the time it would be good? Unfortunately, nobody really knows for sure. Instead I take a drug that uses a different approach to boost dopamine activity celled Requip. It's what's called a dopamine agonist - a drug that makes the receptors that sense dopamine work better. I tried to put this off for a while too because the agonists can have their own side effects that are... a bit disturbing.

For one thing, they don't give it to old people generally because it often causes psychosis, but they aren't so worried about that with me. No they're worried about two different life destroying catastrophes waiting to happen, that I thankfully haven't experienced. First, Requip has a tendency to make people really sleepy. Like "without warning fall asleep during a conversation"or "while driving" sleepy. Second, a small number of people develop weird compulsions that can in the worst cases destroy their lives. For example, my doctor said he has a guy that couldn't stop rapping. Or there was a guy who was a musician who couldn't focus on music because he was compelled to paint (or something like that). Not too bad I guess but then there are the people who start cross dressing, gamble away their life savings, are obsessed with home shopping or become sex addicts. Why this happens in some people is complicated and poorly understood, but remember I said dopamine does a lot of things? Well as it happens, it figures prominently into the brain's computation of risk and reward. It's actually more of a surprise to me that it isn't very common. While it's not my area of neuroscience, this is actually a topic of great interest to me. One of these days, I'll write more about it.

So far so good I guess, but it's awfully unnerving to think that something so far outside my personality could be lurking in there waiting to be brought out by the wrong drug. I'm becoming more relaxed about this these days since I've been on Requip for more than 6 month. But as I ramped up my dose initially it was pretty stressful being vigilant to not pass out on my way to work or while talking to my chair, or to not say something out of line to a grad student. As for whether it helps, I think it does somewhat, but I think I also said before that stress management, exercise, and sleep help as much as drugs. And unfortunately being an Assistant Professor with promotion looming and grants and all that isn't too helpful with those. You win some you lose some.

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