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There needs to be more research on Opioid painkillers and Enkephalins!

Chronic pain is something that most people have to go through every day, such as back pain caused by sciatica or other reasons, headaches, migraines or other neurological pains. To help get people through the difficult pain, several painkillers have been produced and a widely used such as codeine and morphine (sometimes codeine is given as co-codamol, a mix of codeine and paracetamol). 

Even though opioids are great painkillers they are also very addictive and are abused greatly, resulting in many tragic deaths due to drug overdose. More research goes into creating a drug that has the same chemical properties as endogenous opioids but without having a high abuse potential, however ongoing research is difficult and new possible drugs come out to be addictive also, therefore defeating the purpose of the drug.

Where opioid research was originally derived from [1]:

Enkephalins (enkephalins is a Greek word meaning “in the head”) are naturally found in the body. They are a variety of peptides and proteins which are analgesics and consist of 5 amino acids (pentapeptides). There are 2 types of Enkephalins:  Met-Enkephalins [H-TYR-GLY-GLY-PHE-MET-OH] and Leu-Enkephalins [H-TYR-GLY-GLY-PHE-LEU-OH]. Both Enkephalins are pentapeptides (consisting of 5 amino acids) and have preference for the δ(delta)- opioid receptor.  

Enkephalins work as the body’s natural painkillers and are derived from three inactive precursor proteins called proenkephalins. The endogenous opioids also consist of a peptide chain which is responsible for targeting each peptide to particular type of opioid receptor (mu µ, kappa, κ, or delta, δ).

The Enkephalins have a remarkable structure which includes a fragment that is found in opioid drug derivatives. By looking at structure activity relationships (SARs) between morphine and met-enkephalin; there is a tyrosine skeleton in the morphine skeleton which is beneficial for the activity of the drug at the receptor. If it is replaced all activity is lost.

By using this piece of valuable information lots of research goes into developing an analgesic that does not have many side effects and low abuse potential. For example morphine is the mostly used opioid drug however it has difficult side effects such as dysphoria and hallucinations.

So much research goes into creating an analgesic, which is a derivative of the endogenous opioids and with little to no side effects and is not addictive like morphine. Opiates such as morphine and codeine have several side effects such as constipation, nausea, vomiting, itching, and overall negative effects on patients well being even though they are good analgesics.


Pentazocine was synthesized to find a drug that was an effective analgesic and at the same time has low abuse potential. Pentazocine also has mixed agonist and antagonist binding properties at the opioid receptors which has the potential to be addictive and abused. Since this was discovered, pentazocine was given a lower analgesic activity and is not widely used.

Another drug has been approved by the FDA called Zohydro (hydrocodone). However there has been so much criticism around it because it is a prolonged-release drug (meaning it is not metabolised straight away and only a small concentration of drug is released into the blood stream every hour). 

Hydrocodone can treat chronic pain and is prescribed in 50 milligrams which is higher than other hydrocodone containing prescribed medicines.Hydrocodone has been approved by the FDA due to the fact that the “benefits of the product outweigh the risks”[5,6] although critics have been fighting to reverse the approval because Zohydro pill can be misused easily by drug addicts.

To conclude, pain research is a wide open sea and a lot of research goes into opioid painkillers although there are still significant challenges in finding novel pain therapeutics without having the possibility to be misused and little side effects.
[1] G.L Patrick (2009) An Introduction To Medicinal Chemistry, 4th edn., Oxford: OUP.