Selective Opioid Reuptake Inhibitors, that's an interesting idea

Here is a interesting idea about how to treat pain without addicting people to pain killers.

There is some back story to this business that you should know before we discuss why this is a cool idea, though.

Opioid drugs -- like codeine, morphine, and heroine -- act in the nervous system by activating receptors in specific regions of the brain that result in pain relief. If you were wondering though why evolution would be so kind as to make natural receptors to get yourself high, they are there because there are actually natural compounds that act at these receptors and do some similar things -- they provide pain relief when you are stressed or when you need to not think about pain -- like soldiers wounded in battle sometimes don't feel their injuries.

Moving to a different type of drug, there are some antidepressants that work by blocking the transport of neurotransmitters in your brain back into the neurons. Neurons convey information to one another by releasing neurotransmitters. When the message is done, these neurotransmitters are either degraded or taken back up into the cells to be repackaged and used again. Many years ago some drugs were created to treat depression that block the reuptake of these neurotransmitters by blocking their transporters -- thereby extending their lifetime in the synapse. Among other them are some called Selective Serotonin Reuptake Inhibitors (SSRIs) named for the neurotransmitter (serotonin) and their mechanism of action. Prozac is an of SSRI; so are Zoloft, Celexa, and Paxil.

This guy is trying to combine these two ideas. The conventional wisdom was that endogenous opioids were not taken up; rather they were degraded. This guy found a transporter for the endogenous opoids and his idea for pain treatment is that if you blocked it you would get longer life out of ENDOGENOUS opioids in the synapse and increase their action.

The idea that a transport system is involved is itself a novel concept. Conventional wisdom was that an enzyme was responsible for hydrolyzing, or decomposing, opiod peptide, Dr. Ganapathy says. This is the case for at least one neurotransmitter - acetylcholine, implicated in Alzheimer's - which is inactivated by an enzyme, rather than being transported back into the neuron like other neurotransmitters, such as serotonin, which has a role in depression.

But when he watched the activity of opiod peptides, he saw it actively taken back up into the neuronal cells.

Cloning the transporter and dissecting its molecular profile will ultimately provide a model for studying whether naturally occurring or designer drugs block this re-uptake. In fact, the National Institute on Drug Abuse will provide Dr. Ganapathy with a number of synthetic opiod peptides to see whether they are substrates, or blockers, of this transport system.

I guess part of the interest is the belief that by using endogenous opioids there will be less addiction by not overwhelming the system. I am not sure that is the case but it is a very clever idea.

More like this

Prozac (aka fluoxetine) is one of the most successful drugs of all time. Since its introduction as an antidepressant more than 20 years ago, Prozac has been prescribed to more than 80 million people around the world. Currently, approximately one in ten Americans are on an anti-depressant, with the…
For many years, psychiatry has relied on the pharmacological usage of lithium (Li+), alone or in combination with other anti-depressants, as a treatment for bipolar disorder, depression, mania, etc. This, despite the fact that very little is known WHY Lithium works, let alone HOW. The actual…
tags:, mental health, suicide, depression, bipolar disorder, SSRIs, selective serotonin reuptake inhibitors, antidepressants, FDA black-box warning Prozac. Image: Tom Varco After a 2003 report linking selective serotonin reuptake inhibitors, or SSRIs, with increased suicide…
An aromatic ring, two carbons, and a nitrogen will get you a lot of places.From hallucinogens to decongestants to speed, the arylethylamine moiety works because it tickles neurotransmitter receptors. The effects of the assorted monoamine neurotransmitters are as varied as those of the drugs that…

If you were wondering though why evolution would be so kind as to make natural receptors to get yourself high, they are there because there are actually natural compounds that act at these receptors and do some similar things

Don't forget endogenous morphine.

I had no idea that such a thing existed. Thanks.

For those of you stopping in the comments section, the endogenous opioids that I was referring to are small peptides like enkephalins and endorphins that also act on opioid receptors. I was not aware that other small molecules were even synthesized in the body.

I wonder whether this transporter works on them.

Is there a paper where they show opioid uptake by neurons? I only see epithelia cells in the lit. Perhaps it was preliminary data in the grant (since that is what the article is about anyway). Either way, color me skeptical. We know an awful lot about the edogenous opioid system and I find it hard to believe this could have been missed. For instance, why a total lack of autoradiographic binding in MOR knockout mice with 3H peptides. 3H compounds can be effectively used to label SERT and NET. Nonetheless, its a cool idea and we could certainly use alternative methods to modulate the opioid system for pain control.

By Theodore Price (not verified) on 09 Jun 2006 #permalink

it is important to note that depression is painful. Whether it be physical or mental pain it is painful. If it co

By Shaun Long (not verified) on 29 Jan 2012 #permalink