Incredibly close

A little while ago I was moved deeply by a young boy named Oskar. He had lost his dad at 9/11 and all he had left from him was a key. In a heartwarming way he started his quest to find the lock that fitted the key throughout New York City. To help you imagine a nine year old boy doing that, facing his fears and approaching his problem in his own special way I quote him for you: "I started with a simple problem... a key with no lock... and I designed a system I thought fit the problem. I broke everything down in the smallest parts... and tried to think of each person as a number... in a gigantic equation. "

Although I know very little about biology, and even less about hormones and neurotransmitters , I do know that chemical substances in our bodies and the receptors designed for each of them, resemble the key-lock metaphor quite good. That is why I am intrigued by what is going on in pharmacology, especially psychopharmacology. Except for the enormous amount of possibilities to find the exact key to fit a receptor, trying to activate it or block it, dependent of what is wrong in the natural way of brain functioning,  there is also the blood-brain barrier. The blood-brain barrier prevents the brain being infected by many of the viruses and bacteria we encounter in our daily life.

The body uses a few hundred neurotransmitters – small molecules, and neuropeptides – small chains of amino acids to help us function by the chemical message they carry. But without the appropriate receptor, communication of that message discontinues. To make it a little more complex: there are fast and slow receptors and the message may be to stimulate a further response or to block it. The way hormones work, compared to neurotransmitters, is that they tend to work more over time and have different effects on different organs, to name a few.

This last week two events made me elaborate the subject of the chemicals in the brain a little more. The first was an article I have read in New Scientist about narcolepsy. The other was a talk with a friend, while smoking a cigarette together…  Let me first explain some more of the narcolepsy case. Narcolepsy is the opposite of insomnia. People from both groups probably envy each other because their counterpart has something they lack so much. I wouldn’t know what is worse: falling acute asleep when doing something intense like laughing out loud, or feeling constantly exhausted because of sleep deprivation. However, there is hope for both camps thanks to research with Dobermann pinschers. Researchers found a hormone, unknown so far, and called it orexin. One of the effects of orexins is the “stay awake” message they signal. A failing orexin receptor is cause of narcolepsy. In the case of Dobermanns narcolepsy it is suspected to be due to a gene mutation but interestingly in humans it might be due to infections because the onset is later in life and there seem to be a seasonal pattern in patients suffering from it. The human receptors for orexin are not damaged but troubled by the immune system due to a respiratory infection, information supported by chance by the pandemic swine flu. With a lot of effort a better treatment of both narcolepsy and insomnia is to be expected.

Here in the Netherlands it is almost number one priority to “help” people to quit smoking. Recently a new weapon in this battle was extremely supported by health insurance companies and therefore by GP’s: to reimburse a prescription drug with the name Champix. This act of war against nicotine addiction was presented for free until the end of December 2011, after that date one has to pay for this medicine. This drug Champix is the European trade name for varenicline, a substance to reduce withdrawal symptoms of nicotine addiction. After initial success stories the failures are coming to surface now, however not officially but more in talking among smokers about who succeeded or failed to quit smoking.  That’s why I thought about it some more after talking with my friend in the comfort of a break for a smoke, outside of the restaurant we were having dinner. Two out of ten people who are smokers still, that’s about the same number in the bigger population. Although many people quit smoking these days a likewise number of youngsters start doing it. If only they knew how hard it can be to give it up later… The failures of quitting with the help of champix are not so strange because varenicline is a partial agonist, meaning a stimulator, of a certain type of the nicotine-acethylcholine receptor in the brain. The drug stimulates the receptor partially which results in a lesser dopamine release. And because dopamine is a neurotransmitter involved in the reward system it reduces the satisfactory effect of nicotine. Varenicline is also partially an antagonist of nicotine, meaning that nicotine is not fully able to attach to the receptor anymore. In my humble opinion the fact that it works partially is the key factor. It is almost like flipping a key open with a hairpin. The official description of the side effects are pretty deterrent: high risk for depression and suicide, disturbed sleeping pattern and having abnormal dreams and nightmares, headaches and nausea. Some researchers say that it will only help one out of five people to successfully quit smoking. To me that seems a little too low to justify messing in the brain. On the other hand, smoking is also messing in the brain. And like Oskar said: “If you don’t try, you’ll never know”.