What if we could selectively use analgesic effect of opioids and eliminate the addicting side effects?
Till date opioids are considered to be the most effective way of reducing pain but because of its addictive nature many Americans struggled with prescription opioid misuse. The sense of calm and euphoria that these opioids induce leads to serious addictions. But new research suggests a way by which these side effects can be altered.
First opioid misuse epidemic began in 1990s in the United States and by 2015 total 11.5 million cases of prescription opioid misuse were reported. Disease control and prevention centres estimated nearly 500000 deaths from opioid overdose in a span of 20 years. Recent studies shows that ongoing COVID-19 pandemic has intensified opioid abuse which caused 93000 deaths in year 2020.
Many opioid dependant people report use of opioids in order to reduce intensity of physical pain. But till date there are no drugs discovered which provide a considerable amount of analgesic effect but at the same time its free from any potential addictive side effects.
The author is a physical chemist and he worked on finding a way to reduce these side effects. He used computational chemistry to discover how opioids like morphine can be modified to only target the injured region without affecting the brain functioning.
Though there are many classes of opioids but there main chemical structure remains the same which defines it’s biochemical properties. For example hydrocortisone, morphine and oxycodone show similarity in their structures and belongs to the chemical class of epoxymorphinan.
So these opioids act by activating the amine group and making it positively charged. This reaction is easily carried out using the water-based environment such as blood streams.
This positively charged structure is active in nature. Unless and until this positive charged is not established, opioids are chemically inactive and show no effect on the body.
Acidic conditions of human body are favourable for opioid activation. Which results in effect of opioids throughout the body and not on specific site.
So how can we make these opioids less addictive?
Recently it was proposed that injured tissues are slightly more acidic as compared to healthy tissues because of acidosis which results in lactic acid accumulation. This resulted in a hypothesis that opioids can be altered in such a way that they’ll only be activated by the acidic environment present at the site of injury and not anywhere else in the body.
This theory was practically studied using Fentanyl. It was found out that introduction of fluorine atom near amine group can possibly reduce the acidity range in which fentanyl attains a positive charge. Which will make it less active at other healthy parts of the body.
This means that the drug is ‘turned on’ only in the injured tissues where acidity is more as compared to healthy tissues.
This also showed decrease in other side effects and yielded positive results.
Recently same research is going on for morphine. Until now this hypothesis has been tested only in lab settings and it not might be pharmacies for a while. But this hypothesis is a promising avenue in the field of pharmaceutical sciences.
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Blog by - Ketki Bhave
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