Wednesday, May 21, 2008

On Sexual Compulsions and Restless Legs

If you watch network television on occasion, you've probably seen advertisements for medications like Requip or Mirapex that are marketed as a treatment for Restless Leg Syndrome (RLS), a weird, creepy-crawling feeling that usually occurs at night and makes sufferers feel as though they must constantly move their legs to attain comfort. Particularly severe cases can greatly disrupt sleep cycles or even lead to insomnia. Now, if you're like me (shut up), while watching these commercials you've probably wondered why some of the side effects listed include "intense gambling or sexual urges or other impulsive behaviors." What could these things possibly have to do with disorders involving involuntary motor-functions? My first reaction to encountering these weird side effects was a vague sort of dread regarding our forays into altering brain chemistry. Just what exactly is Mirapex tweaking deep within our cortices?

Turns out ropinirole (Requip) and pramipexole (Mirapex) are members of a class of drugs known as dopamine agonists, which means that they attach to dopamine receptors on various brain structures and mimic the effects of the neurotransmitter dopamine. (As an interesting aside, these drugs are specifically non-ergoline dopamine agonists, which means they do not involve ergoline alkaloids, a class of drugs that includes the infamous LSD and other hallucinogenics). Now, dopamine agonists are primarily used to treat Parkinson's disease, and ropinirole and pramipexole are no exceptions. In fact, they were originally created to treat Parkinson's disease, and are merely provided in smaller doses to treat RLS. Apparently, the roots of RLS may be very similar to those of Parkinson's disease, although on a much smaller (and apparently non-progressive) level. Here's where the fun brain science begins.

Parkinson's disease is caused by a decrease in dopamine production in the substantia nigra, a portion of the basal ganglia. The basal ganglia is an extremely important deep-brain structure and is responsible for far more brain activity that can be discussed here. What's important is that the dopamine that is normally produced by the substantia nigra usually binds with dopamine receptors on the striatum, another portion of the basal ganglia. There are four types of dopamine receptors, and it seems that D2 and D3 are the most directly related to Parkinson's symptoms (this info will be important in a minute). Though it regulates other things (which we'll touch upon shortly), one of the main functions of the striatum is the planning and regulation of movement. A Parkinson's afflicted brain isn't producing enough dopamine to activate the striatum sufficiently, which in turn results in decreased activation of the motor cortex, producing erratic, unintentional tremors, muscle rigidity and a variety of other motor problems. So on a smaller level, a similar dopamine disruption is responsible for RLS, and the dopamine agonist medications act to stimulate the receptors in the striatum that aren't being activated through normal brain chemistry.

Ok. So the striatum is also involved in some other sneaky stuff that is really pretty far removed from motor function, and this is where dopamine agonists can start to alter behavior in ways that at first seem quite random. It seems that the striatum also regulates a lot of processes related to something called "executive function." Executive function involves things such as planning, abstract thinking, selecting sensory information, and, getting closer to the core of our inquiry, selecting appropriate actions and inhibiting inappropriate ones. It is also largely involved with processing stimuli involved in reward. It seems that the striatum is activated when a person is presented with stimuli that are new, aversive, unexpected or particularly intense. We can now start to see how sexual compulsions, strange gambling urges and things like overeating are related to subtleties in chemistry in this particular region of the brain. Problems with impulse control are also frequently exhibited in people with Parkinson's disease. These issues are clearly related to feelings of reward (the extreme gratification of orgasm, the experience of winning or the exhilaration of taking risks, the pleasure of indulging in certain foods) and are also highly likely to involve stimuli that could be classified as "novel," "intense," or (depending on how depraved you are) "aversive." These functions appear to be closely related to the D3 receptors on the striatum. And of the two related receptors that Requip and Mirapex bind to, guess which one they like the best? You got it. D3.

So it would appear that if you screw with the dopamine receptors on the striatum, some sort of weird, screwy feedback loop can result, where people have less ability to inhibit their actions, which frequently results in the sorts of behavior that actually greatly stimulate the striatum in the end. This seems to be due to the fact that dopamine agonists like Requip and Mirapex actually decrease the sensitivity of the dopamine receptors over time. Logically, this increases the symptoms associated with the striatum. A really sucky situation can develop where an individual not only cannot produce the required dopamine, but also cannot accept dopamine (or agonist medications) in areas that it is required. It seems likely that, in the cases where an individual is taking a dopamine agonist for RLS and experiences odd compulsions, the medication might actually be altering the dopamine receptors' ability to bind with neurotransmitters, including what dopamine they are still naturally producing. Ah, the joy of medication!

Some other uncommon side effects also tie in closely with the functions of the striatum: hallucinations, confusion, paranoia, memory loss, abnormal thinking, abnormal dreams, and decreased sex drive.

And that's pretty much it. Does it ease my feeling of dread? No, not really. But it is interesting to see how trying to target one problem in the brain can inadvertently effect so many other areas of cognitive function. It also speaks to the mystery of our own brains when investigations such as these show how one small part of the brain can be responsible for such a diverse array of functions. Immensely cool stuff.

Anyway, I think I'm going to stick with aspirin for now. My brain doesn't need any more help being bizarre.


Anonymous said...

Having read much on the topic, perhaps it is time to tell my story. Married for 27 years, my wife was prescribed myrapex for restless leg syndrome and I believe it ended my marriage. Within six months of taking the drug, she began to experience compulsive sexual urges which led her to a swinging lifestyle. With the internet as a vehicle to meet all types of sexual partners this compulsive behavior ultimately caused the destruction of our family unit. She showed little concern for the reality of what she was doing and could not control nor wanted to control this new found euphoria. Since I refused to join her in this alternative lifestyle she decided to "go it alone", trashing our marriage and life as we knew it. I suppose there are many who take the drug and that the effects are widely different, and I also suppose that , like me, they are hesitant to reveal or be the focus of such attention. But the compulsive sexual behavior is nothing to take lightly. It may sound funny but believe me when I tell you that the side effects are REAL and uncontrolable. Like so many other addictions... it just took control of her and made her willing to erase all she had built to satisfy these urges. Laugh if you wish, but pray it does not happen to anyone you care about.

Dan said...

I'd like to apologize if the light-hearted tone I frequently write with makes it seem as though I'm poking fun at the issue, as that's truly not the case. I understand that the symptoms are very real and can have devastating effects on people's lives.

The purpose of writing this short piece was more to delve into the mechanics of how a prescription for one ailment can produce new ailments that seem very far removed from the one being treated. It was purely out of an interest in how these drugs interact with and alter the brain that I wrote this entry, not a desire to poke fun of people that take dopamine agonists and the occasionally bizarre results.

To the writer of the anonymous comment before this one, I'm truly sorry for the loss you experienced as a result of these side-effects. I'd also like to thank this person for providing a "reality check" of sorts, by illustrating just how serious the consequences can be when taking any of the slew of pharmaceuticals that jump out at us from the TV screens on a daily basis.

Again, the post was not meant in jest, only to sift through something I found interesting and maybe present it to others who had maybe wondered about the same things.