Introducing... Morphine Sulphate - it's dreamy!

Happy Friday, All. This month I have the pleasure of introducing you to morphine sulphate: it's dreamy!


Class


Morphine sulphate belongs to the class of drugs known as opioids.

Mechanism of Action


As far as we are aware, there are three different opioid receptors in the body: mu (µ), delta (δ) and kappa (κ). This is interesting for a couple of reasons. Firstly it indicates the presence of endogenous opioid-like chemicals (i.e. they occur naturally, within our bodies). And secondly, it suggests that these opioid-like chemicals can produce a broad range of effects.


Wow! So I can create morphine?


No... not quite. The three naturally-occurring opioid-like peptides are: endorphins (this word is a portmanteau of “endogenous morphine”), enkephalins and dynorphins. You’ve probably heard of endorphins – they're the “feel good” hormones that have a high affinity for the µ receptors. That means that although they’ll bind with the other receptors, they’d prefer to hang out with µ. Don’t feel too sorry for the other guys though – enkephalins usually buddy up with δ and the dynorphins are fond of keeping the κ receptors happy.

So what happens when one of these "naturally-occurring opioids" latches onto a receptor?


Well, the receptors are situated on neurones (nerve cells responsible for transmitting messages around the body) and when one of the "naturally-occurring" opioids binds to it the action potential of the cell is changed.


What on earth is an “action potential”?!


I’m glad you asked. Think of it like the amount of force required to tip over a glass of water. If the force applied to the glass is too weak, we don't reach the crucial tipping-point and nothing happens. However, if sufficient force is applied, then the glass will tip over and the water will spill out. In relation to our neurone, once the action potential ("tipping point") has been reached, then neurotransmitters are released, and a message is transmitted.


The action potential (i.e. the level of force needed to cause an effect) can be altered. To return to our analogy, we can make it easier or harder to tip the glass of water over e.g by changing the slope of the table or by putting a weight into the glass. This is where the opioid receptors on the neurone (and peptides that bind to them) come into play. Some chemicals will reduce the action potential - this makes it easier for an electrical stimulus reach the action potential and cause the release of neurotransmitters. Opioids increase the action potential - this makes it less likely for an action potential to be reached, and therefore for the neurone to release its neurotransmitters messengers.


OK - so if I have lots of naturally-occurring opioids in my system, my neurones will fire less frequently. What does that really mean? How does it affect me?

The impact of a naturally-occurring opioid joining forces with one of the opioid receptors will depend –broadly – on two key factors:

  1. Where it’s located. Unsurprisingly, the ones in your brain will have a different effect to the ones in your intestines!

  2. Which neurotransmitter "messengers" are released. There are lots. Once these guys are let loose, they also encourage or inhibit other proteins, which can encourage or inhibit yet more proteins... You get the point. It can get complicated!

OK - so I get the impression that a really wide range of things can happen depending on which peptides and receptors are involved, and where they are located... but could you give me any examples?


Sure. Let's run through the predominant locations and “responsibilities” of the µ, δ and κ receptors and talk about what happens when morphine is one the scene.

µ receptors (these are the ones that are usually modulated by endorphins).

  • In the brain, these are found in greatest number in the periaquaductal gray region, which is responsible for modulating our perception of pain. By interacting with the µ receptor, morphine interrupts this “pain message” to produce an analgesic (painkilling) effect.

  • They are also found in the nucleus acumbens in the brain, a region that is responsible for our sensation of pleasure. The feeling of pleasure is associated with reward-seeking behaviour, which can manifest itself as euphoria and addiction – both of which are well-recognised effects of opioids.

  • We also find this receptor in the intestinal tract, where activation reduces the motility of the gut. This is what is responsible for a troubling side-effect of morphine, particularly for those who take opioids long-term: constipation.

As an aside, I find it a bit disappointing that the same receptor is responsible for all of these effects. Wouldn't it be great if we could achieve pain-relief without constipation and the problem of addiction? Unfortunately, the representation of µ receptors in these two areas suggests that all of these effects are inextricably linked.

δ receptors (these are the ones that are often modulated by enkephalins).


By breeding mice that don’t exhibit these receptors, scientists have found that the δ receptor is associated with our management of stress. We think that this is probably because it results in the release of the neurotransmitters noradrenaline and serotonin. At this receptor, enkephalin (and morphine) will cause a reduction in both anxiety and depression.


κ receptors (these ones are usually modulated by dynorphins).


These receptors are also expressed in the periaquaductal gray (the pain centre), as well as in pain neurones distributed in the spinal cord and around the body. They don't quite behave as you might expect, because although some of these sites will produce analgesia... others will increase an individual’s sensitivity to pain. We think that they may be associated with complex issues like neuropathic pain.


In addition the κ receptor is located in the hypothalamus – this region of the brain controls a whole host of activities including stress, attachment behaviour and appetite. Don't forget that opioids will make release of neurotransmitters less likely. So, morphine acting on this receptor will cause dysphoric adverse effects like depression, dissociation, delirium, hallucinations and hunger.

Indication


Morphine sulphate is used in the treatment of severe pain.

Random Fact


Morphine can be naturally derived from the poppy (Papaver somniferens) and is named after Morpheus, the Greek god of sleep.

Thanks for reading. Have a marvellous weekend, wherever you are!