[2] These sequences fold into tertiary structures with high specificity and affinity for the μ-opioid receptor, binding it exclusively and strongly.

[2] The specific amino acids in these sequences dictate the folding and resultant behavior, namely the ability to bind μ-opioid receptors, of these molecules.

[3] In other instances, endomorphin binding causes excitation, where its activation of phospholipase C and adenylyl cyclase initiates an increase in calcium ion concentration, cellular depolarization, and the release of norepinephrine and serotonin.

[7] The location of endomorphin activity has been isolated using radioimmunoassay and immunocytochemistry within human, mice, rat, and monkey nervous systems.

[2] Alternately, endomorphin-2 is predominantly found in the spinal cord, specifically in presynaptic terminals of afferent neurons in the dorsal horn region.

[4] In vitro assessment of endomorphins as analgesics reveals similar behavior to morphine and other opiates, where drug tolerance leads to dependence and addiction.

Other side effects common to opiates such as vasodilation, respiratory depression, urinary retention, and gastrointestinal reaction develop.

[4] Despite their pharmaceutical aptitude, the low membrane permeability and vulnerability to enzymatic degradation of endomorphins limits their incorporation into drugs.

As a result, endomorphin analogues are being generated to allow transport across the blood brain barrier, increase stability, and reduce side effects.