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Opioid antagonists

Opioid antagonists


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Opioid antagonists

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Content Reviewers:

Yifan Xiao, MD

Opioid antagonists, like the name suggests, are medications used mainly to reverse the side effects of opioid agonists and to prevent opioid addicts from relapsing after they’ve recovered.

Now, all opioids work by binding to opioid receptors in the brain, spinal cord, and gastrointestinal tract.

Some are endogenous, meaning they are produced naturally by the body, like endorphin, short for endogenous morphine.

But others are exogenous, meaning they come from outside the body, like heroin and morphine, which come from the opium poppy; a flowering plant that oozes a milky white liquid.

To understand how opioids work, let’s zoom into a region of the brain tissue that has opioid receptors.

Normally, in the absence of endorphins, inhibitory neurons secrete a neurotransmitter called gamma-aminobutyric acid, or GABA, that prevents nearby neurons from releasing neurotransmitters like dopamine, serotonin, and norepinephrine.

Now, let’s say someone goes to play a rigorous game of badminton. Exercise releases endorphins which activate the three major opioid receptors located on the inhibitory neurons, called the mu, kappa, and delta receptors.

As endorphins bind to these receptors, they block the inhibitory neuron from releasing GABA, allowing the dopamine, serotonin, and norepinephrine secreting neurons to freely unload their neurotransmitters, which then gets picked up by another neuron in the same area.

Norepinephrine and serotonin release takes place in pain processing regions of the brain like the thalamus, brainstem, and spinal cord, resulting in a decreased sensitivity to pain.

When dopamine release takes place in reward pathway regions like the ventral tegmental area, nucleus accumbens, and prefrontal cortex, the result is a calming sensation that feels really good.

However, there are also opioid receptors throughout our body, like in the gastrointestinal tract.

So, when a person receives a dose of morphine, it could also result in a series of unwanted side effects, like nausea, vomiting, and constipation.

However, the most dangerous side effect is respiratory depression caused by stimulation of the respiratory centers located in the medulla.

This happens when a person overdoses on an opioid like morphine or heroin.

Respiratory depression can be life-threatening and should be treated right away - because the person can literally stop breathing.

Now in order to treat opioid overdoses, we can use opioid antagonists like naloxone, naltrexone, methylnaltrexone, and alvimopan.

These medications bind strongly to opioid receptors without activating them.

Since opioids are binding and unbinding to receptors constantly, once an opioid releases its hold on a receptor, naloxone can simply sneak in and bind more strongly.

Naloxone has a rapid onset and short duration of action of 1 to 2 hours.

So when it’s given intravenously, it can reverse the effects of opioids within minutes, potentially saving a person’s life.

In addition, when women in labor need to take opioid analgesics, the medication can pass through the placenta, causing respiratory depression in the baby.

Naloxone can also reverse this effect and save the baby’s life.

Another use of naloxone is to detect when a person is opioid dependent.

A person who is a chronic user of opioids like morphine or heroin can develop tolerance.


Opioid antagonists are drugs that strongly bind to opioid receptors and prevent their activation. They are used to treat opioid overdose and addiction, and can also help to reverse respiratory depression and other adverse effects of opioids. Examples include drugs like naloxone, naltrexone, methylnaltrexone, and alvimopan.

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