LIT-002 is a small-molecule oxytocin receptor agonist which is under investigation for potential medical use.^[1][2][3]

It is a highly potent full agonist of the oxytocin receptor, with an EC₅₀Tooltip half-maximal effective concentration of 0.15nM.^[1][2][3] The drug is an improved analogue of the earlier drug LIT-001, with 300-fold greater potency than LIT-001 and 2.6-fold greater potency than oxytocin as an oxytocin receptor agonist in vitro.^[3] It is the most potent oxytocin receptor agonist described to date.^[3] In addition to its oxytocin receptor agonism, LIT-002 is a highly potent agonist of the vasopressin V₂ receptor (EC₅₀ = 0.25nM) and a very weak modulator of the vasopressin V_1A and V_1B receptors (EC₅₀ = 966nM and 760nM, respectively).^[3] The drug is more selective for the oxytocin receptor over the vasopressin receptors than LIT-001.^[3] LIT-002 enhances social interaction in multiple models of autism in rodents.^[3] Due to its vasopressin V₂ receptor agonism, LIT-002 produces antidiuretic effects.^[3] However, co-administration of urea with LIT-002 can counterbalance the effect, and the off-target antidiuretic effects are described as manageable.^[3]

It is orally active in rodents.^[3] The drug's pharmacokinetics, for instance blood–brain barrier permeability, are not fully optimal, but it is nonetheless centrally active and with high potency.^[3] Small-molecule oxytocin receptor agonists like LIT-001 and LIT-002 have greatly improved pharmacokinetic and drug-like properties compared to oxytocin itself.^[3]

The chemical synthesis of LIT-002 has been described.^[3] Various analogues of LIT-002 such as LIT-001 among others have been described.^[3][2][4]

LIT-002 was developed by Marcel Hibert and colleagues at the Laboratory for Therapeutic Innovation (LIT) at the University of Strasbourg in France and by the Centre National de la Recherche Scientifique (French National Centre for Scientific Research).^[1][2][3] It is now being developed by the startup pharmaceutical company Occentis Pharmaceuticals.^[1][3] Potential therapeutic applications of LIT-002 include treatment of autism, alcoholism, opioid addiction, and neuropathic pain.^[1][3]

• Oxytocin receptor agonist
• List of investigational autism and pervasive developmental disorder drugs

• Occentis Pharmaceuticals