Partial Agonist

What is a Partial Agonist?

A partial agonist is a drug that, when bound to a receptor, only partially activates that receptor.

This is in contra-distinction to full agonists which, when bound to a receptor, fully activate the receptor. If you look at a dose response curve, in the case of full agonists, as the dose increases so too does the clinical effect. In the case of partial agonists, they behave differently.

At low to moderate doses they behave as functional agonists in that as the dose increases then so too does the clinical effect, albeit at a lower rate when compared with the full agonist curve.

However at high doses they behave as antagonists in that any further dose increase results in no additional clinical effect. Therefore in the case of partial agonists a ceiling effect occurs wherein beyond a certain dose no further effect is seen.

Now, what is this all about? Why am I bothering to write about this?

Well the answer is prescription opioid abuse.

More people died last year from prescription drug misuse than did on the roads in Victoria.

We as doctors are killing our patients with our prescriptions. Prescription opioids play a big part in this mortality. Most clinically used opioids are full mu opioid receptor agonists. Therefore as the dose goes up so too does the risk of respiratory depression and death.

Imagine if there was a drug which was a great pain killer, just like the commonly used opioids, but which was much less likely to cause respiratory depression and death. Wouldn’t you want to use that drug? Wouldn’t you want to at least know more about it?

Well, there is an opioid that is a partial agonist at the mu opioid receptor. Because it is a partial agonist it has a ceiling effect which occurs below the threshold for respiratory depression in most healthy adults. Therefore it is much less likely to cause respiratory depression and death.

Just think about how much safer this drug would be as compared to all the other full mu opioid receptor agonists that are commonly prescribed, including morphine and oxycodone.

I cannot understand why we as doctors are not prescribing more of this safer drug when faced with the horrifying statistics of mortality associated with prescription opioid misuse.

Want to know what this drug is?

It’s called buprenorphine. It comes as a “Norspan” patch, a “Temgesic” sublingual pill, and a “Suboxone” sublingual film.