The Endogenous Opioids

Propeptides

The precursor proteins that undergo enzymatic processing to produce opioid peptides.

ex) Prodynorphin, Pro-opiomelanocortic, Proenkephalin, Pronociceptin

Opioids as Neuromodulators

Opioids are often co-released with other neurotransmitters and may enhance, reduce, or prolong the action of the neurotransmitter or produce changes in membrane potential.

Opioid Receptor

The metabotropic receptors that are inhibitory when activated. These effects can be a decrease cAMP, increase of K⁺ efflux, and decrease of Ca²⁺ influx.

1. μ (mu)

2. δ (delta)

3. κ (kappa)

4. Nociceptin/orphanin’ FQ receptor

(NOP-R)

Endorphins

The endogenous opioids that originate primarily in the pituitary gland.

Enkephalins

The endogenous opioids that originate primarily in the adrenal medulla and other peripheral locations.

Dynorphins

The endogenous opioids that are widely synthesized in the CNS, such as the hypothalamus, medulla, pons, etc.

Opioids

The class of endogenous compounds that produce pain relief and other physiological effects, such as body temperature and endocrine function.

Opioid Agonists

The drugs that bind to opioid receptors and activate them, mimicking the effects of endogenous opioids.

ex) Heroin, Fentanyl

Opioid Antagonists

The drugs that block opioid receptor activity and prevent or reverse the effects of opioids.

ex) Naloxone, Naltrexone

Endocannabinoids

The naturally occurring lipid-based neurotransmitters that interact with the endocannabinoid system to regulate physiological processes. These molecules can readily pass through the plasma membrane and are synthesized in response to depolarization. They can diffuse out and serve as retrograde neurotransmitters. They help in regulating hunger, eating behavior, pain regulation, memory formation, etc.

2-arachidonoylglycerol (2-AG)

The primary endocannabinoid that plays a role in pain modulation, inflammation, and neuroprotection.

Anandamide (AEA)

The endocannabinoid that plays a role in mood regulation, appetite, and pain relief.

Fatty acid amide hydrolase

The enzyme responsible for metabolizing anandamide.

Monoacyl-glycerol lipase

The enzyme responsible for metabolizing 2-AG.

CB₁ receptor

The metabotropic cannabinoid receptor located in the CNS that inhibits cAMP formation as well as voltage-sensitive Ca²⁺ channels while opening up K⁺ channels. They are located on axon terminals and act as heteroreceptors.

CB₂ receptor

The metabotropic cannabinoid receptor located in the immune system and other tissues such as bone and GI tract that inhibits cAMP formation as well as voltage-sensitive Ca²⁺ channels while opening up K⁺ channels.

∆9-Tetrahydrocannabinol (THC)

The drug that is a partial CB₁ and CB₂ receptor agonist and the main psychoactive compound in cannabis that mimics the effects of endocannabinoids.

Cannabidiol (CBD)

The drug that is a partial CB₁ and CB₂ receptor agonist that mimics the effects of endocannabinoids. It has a lower affinity than THC.