Structural transformation of κ-opioid receptor agonist (U50 488H) to quaternary ammonium salt

AIM:To reduce the potential addiction of U50 488H, a κ-opioid receptor agonist, by structurally transforming it to its quaternary ammonium salt incapable of going through the blood-brain barrier. METHODS: U50 488H was transformed to its quaternary ammonium salt, which was identified with mass spectrometry. The concentrations of U50 488H and its quaternary ammonium salt in serum and brain tissue were determined by chromatography. RESULTS: The quaternary ammonium salt of U50 488H was a faint yellow powder and mass spectrometry proved it to be C20H29Cl2IN2O, with remarkably increased solubility than U50 488H. Chromatography detected U50 488H in both serum and brain tissue fluid of the rats after i.v. injection. However, quaternary ammonium salt of U50 488H was detected only in serum and not in brain tissue. CONCLUSION: The structural transformation of U50 488H to its quaternary ammonium salt incapable of going through the blood-brain barrier reduces the potential addiction of U50 488H.