Opioid agonists, mixed agonist-antagonists and partial agonists

Opioid agonists are medications used mainly to control acute or chronic pain in particular situations.

Some of them are also used to treat diarrhea and cough. When treating pain, the goal should be to use short-acting opioids at the lowest effective dose for just a few days, and slowly increase their dose only as needed.

As a class, opioids share one thing in common, they bind to opioid receptors in the brain, spinal cord, and gastrointestinal tract.

Some are endogenous, meaning they are produced naturally by the body, like endorphins, 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 get 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.