Therapeutic Potential of Salvinorin A and Its Analogues in Various Neurological Disorders.

ASalvinorin A is a neo-clerodane diterpenoid.It is not soluble in water or lipids, which is a significant hurdle for clinical deliverable formulation.In contrast to classic KOR ligands, salvinorin A is not an alkaloid, indicating that it cannot be rendered into a salt to improve solubility for drug development purposes.The melting point of salvinorin A is high (238-240 °C) [5], and the powder form of salvinorin A is relatively stable.However, once taken, salvinorin A is hydrolyzed quickly by esterases due to the hydrolyzable nature of the ester functional group at C2, which is an advantage for clinical practices that need the benefits of a KOR agonist with a shortacting property and a short duration of hallucinatory or dissociative side effects. Analogues of Salvinorin AMany analogues of salvinorin A have been developed to target different opioid receptors [4,7].The most common alteration to the structure of salvinorin A is the replacement of the acetate at C2.Many different functional groups at this position, including carbonates, carbamates, alternative ester groups, ethers, amines, amides, sulfonic esters, sulfonamides, thioesters, and