Oxytocin receptor agonist

An oxytocin receptor agonist is a compound that acts as an agonist of the oxytocin receptor.^[1][2] They include peptides like oxytocin and carbetocin and small-molecules like LIT-001 and LIT-002.^[1][2] Peptide oxytocin receptor agonists are used medically to induce labor, promote lactation, and for certain other uses.^[3]

Oxytocin receptor agonists are of theoretical interest for the potential treatment of neuropsychiatric disorders with social symptoms, such as autism, social anxiety, and psychopathy.^[1][2][4] Small-molecule oxytocin receptor agonists are considered to be more promising for such uses due to better potential pharmacokinetic profiles, such as blood–brain barrier permeability, elimination half-lives, and oral bioavailability.^[1][2]

The entactogen MDMA robustly increases oxytocin levels, by 4- to 8-fold, and this is thought to be involved in its entactogenic effects, including its euphoric, anxiolytic, and prosocial effects.^[5][6][7][8] In people with arginine vasopressin deficiency (central diabetes insipidus), who also have oxytocin deficiency, MDMA fails to elevate oxytocin levels and shows greatly blunted entactogenic effects.^{[9][8][10][11]} Accordingly, carbetocin partially substitutes for MDMA in drug discrimination tests in rodents, whereas the peptide oxytocin receptor antagonist atosiban interfered with MDMA discrimination.^[12][13] In addition, oxytocin receptor antagonists have been found to block the prosocial effects of MDMA in rodents.^{[5][7][14][15]}

Social isolation has been found to decrease oxytocin receptor levels in rodents, whereas levels of oxytocin were unchanged.^[16] The decreased oxytocin receptor levels were associated with behavioral changes including increased aggression and anxiety-like behavior, hyperactivity, and diminished social behaviors and memory.^[16] Exogenous administration of oxytocin receptor agonists like oxytocin or TGOT was able to partially reverse the behavioral changes.^[16]