Interaction of thioridazine with ocular melanin in vitro.
The aim of this study was to examine in vitro the binding capacity of thioridazine to natural melanin isolated from pig eyes and to synthetic DOPA-melanin. The amount of drug bound to melanin was determined by the use of the UV spectrophotometric method. Studies on the kinetics of thioridazine-melanin complex formation showed that the amount of drug bound to melanin increases with increasing initial drug concentration and the prolongation or incubation time, allowed to attain equilibrium state after about 24 hours. Binding parameters, i.e., the number of independent binding sites and the association constants were determined on the basis of Scatchard plots. For thioridazine-ocular melanin and thioridazine-DOPA-melanin complexes two classes of binding sites were found with the association constants K1 approximately 2 x 10(4) M(-1) and K2 approximately 9 x 10(2) M(-1). For ocular and synthetic melanin complexes with thioridazine no significant differences in the values of binding parameters were found. The demonstrated ability of thioridazine to interact with melanin in vitro is discussed in relation to this drug ocular toxicity in vivo.
Buszman
Ewa
E
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland.
Rózańska
Renata
R
D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry*; D004295:Dihydroxyphenylalanine / Q000737:chemistry; D005123:Eye / Q000737:chemistry*; D007202:Indicators and Reagents; D007700:Kinetics; D008543:Melanins / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013552:Swine; D013816:Thermodynamics; D013881:Thioridazine / Q000737:chemistry*
D014150:Antipsychotic Agents; D007202:Indicators and Reagents; D008543:Melanins; D004295:Dihydroxyphenylalanine; D013881:Thioridazine