The classification of molecules as endorphins is based on their pharmacological activity, as opposed to a specific chemical formulation.

All three preferentially bind to -opioid receptors.

The principal function of endorphins is to inhibit the communication of pain signals.

Endorphins may also produce a feeling of euphoria very similar to that produced by other opioids.

They isolated enkephalins (from the Greek, cerebrum ) from pig brain, identified as Met-enkephalin and Leu-enkephalin.

This came after the discovery of a receptor that was proposed to produce the pain-relieving analgesic effects of morphine and other opioids, which led Kosterlitz and Hughes to their discovery of the endogenous opioid ligands.

Research during this time was focused on the search for a painkiller that did not have the addictive character or overdose risk of morphine.

Snyder isolated morphine-like peptides from calf brain.

Eric J. Simon, who independently discovered opioid receptors, would later term these peptides as endorphins.

This term was essentially assigned to any peptide that demonstrated morphine-like activity.

In 1976, Choh Hao Li and David Chung recorded the sequences of -, -, and -endorphin isolated from camel pituitary glands for their opioid activity.

They identified that -endorphin produced strong analgesic effects.

Wilhelm Feldberg and Derek George Smyth in 1977 confirmed this claim, finding -endorphin to be much stronger than morphine.

In addition, they found that it is completely removed from opiate receptors by naloxone, an identified morphine antagonist.

Opioid peptides are classified based on their precursor propeptide: all endorphins are synthesized from the precursor proopiomelanocortin (POMC), encoded by proenkephalin A, and dynorphins encoded by pre-dynorphin.

Thus, endorphin is a contraction of endo(genous) (mo)rphin (morphin being the old spelling of morphine).

Some studies have characterized -endorphin activity as similar to that of psychostimulants and -endorphin activity to that neuroleptics separately.

In the PNS, -endorphin is the primary endorphin released from the pituitary gland.

Endorphins inhibit transmission of pain signals by binding -receptors of peripheral nerves, which block their release of neurotransmitter substance P.

In turn, inhibition of GABA increases the production and release of dopamine, a neurotransmitter associated with pleasure.

For example, endorphin release is responsible for producing the euphoric state in cases such as runners high, sex, orgasm, listening to music, and eating appetizing food such as chocolate.

Research has demonstrated that meditation by trained individuals can be used to trigger endorphin release.

Laughter may also stimulate endorphin production and elevate ones pain threshold.

Endorphins may contribute to the positive effect of exercise on anxiety and depression.

The same phenomenon may also play a role in exercise addiction.

Regular intense exercise may cause the brain to downregulate the production of endorphins in periods of rest to maintain homeostasis, causing a person to exercise more intensely in order to receive the same feeling.

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Comments: -Endorphin is the highest potency endogenous ligand.

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Endorphin Game