[Mechanism of interaction between risperidone and tea catechin (2) influence of presence of galloyl group in catechin on insoluble complex formation with risperidone].
The influence of the presence of a galloyl group in catechin on complexation with risperidone (RISP) was examined using (--)-epigallocatechin gallate (EGCg) and (--)-epigallocatechin (EGC), which are present in green tea as tea catechins. By quantitative analysis using HPLC, it was found that EGCg formed an insoluble complex with RISP for concentration dependence, whereas EGC did not. The large contribution of the galloyl group of catechin to form an insoluble complex with RISP was recognized in this study. In a molecular modeling study, it was found that the EGCg-R complex (EGCg with RISP) formed three hydrogen bonds between the hydroxyl groups of EGCg and the two N atoms and an O atom of RISP. The hydrogen bond between the hydroxyl group of the galloyl ring in EGCg and the N atom of the piperidine ring in RISP stabilized EGCg-R more energetically. The EGC-R complex (EGC with RISP) also formed three hydrogen bonds, but the N atom of the piperidine ring in RISP did not participate in hydrogen bond formation. According to the calculation using the COSMO-RS method, the water solubility of the EGCg-R complex was 1/26 that of the EGC-R complex. Therefore, the EGCg-R complex was difficult to dissolve in water. In the (1)H-NMR spectra of RISP in DMSO-d(6), although chemical shifts of protons near the N atom on the piperidine ring moved downfield on the addition of EGCg, no change in chemical shifts of these protons was observed on the addition of EGC. Therefore, based on these results, the galloyl group of EGCg contributes to the formation of an insoluble complex between tea catechin and RISP, and this insoluble complex is stabilized by the hydrogen bond between the hydroxyl group of the galloyl ring in EGCg and the N atom of the piperidine ring in RISP.
Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. ikeda@fukuoka-u.ac.jp
Hirohito
H
Ikeda
Hanae
H
Moriwaki
Tomonori
T
Matsubara
Miho
M
Yukawa
Yukiko
Y
Iwase
Eiji
E
Yukawa
Hatsumi
H
Aki
D014150:Antipsychotic Agents; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004355:Drug Stability; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D008958:Models, Molecular; D018967:Risperidone / Q000737:chemistry*; D012995:Solubility; D013662:Tea / Q000737:chemistry
D014150:Antipsychotic Agents; D046911:Macromolecular Substances; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; C057580:gallocatechol; D018967:Risperidone