AY-1001

Lithium is recommended as a first-line option for maintenance therapy of bipolar disorder (BD), due to its reliable mood-stabilizing property and benefits for relapse and suicide prevention. However, its clinical applications are still facing challenges, considering the relatively narrow therapeutic window, poor ability to cross the blood-brain barrier, and various side-effects ranging from mild nonspecific to life threatening symptoms. To overcome these challenges, the discovery and development of novel lithium-containing candidates with better kinetics profiles is urgently needed. We previously synthesized and patented a novel lithium-containing coordination compound AY-1001 (C₉H₁₆LiNO₄), which shows antimanic activity in animal model. In this study, the pharmacokinetic and toxicokinetic properties of AY-1001 were further determined. Pharmacokinetic data demonstrated that AY-1001 has a faster onset of action, a shorter half-life, and a higher blood-brain barrier transmission rate, compared with the traditional inorganic lithium carbonate. In addition, toxicological data indicated that AY-1001 exhibits low toxicity in SD rats and beagle dogs. These findings suggest that AY-1001 has the potential to improve therapeutic effects and reduce side effects, providing a strong scientific basis and promising strategy for the further development of organic lithium-containing mood stabilizers.