Method for optical resolution of racemic homochlorcyclizine and comparison of optical isomers in antihistamine activity and pharmacokinetics.
A method was developed for semi-preparative scale enantioseparation of racemic homochlorcyclizine (HCZ) by high performance liquid chromatography (HPLC) on Chiralcel OD column. The best resolution was achieved using an eluent composed of n-hexane plus 0.2 M isopropylamine. By this method, about 5.0 mg of racemic HCZ could be resolved completely in one run. The optical purity of the enantiomers were both greater than 99.9%. The studies of antihistamine activity on guinea pig ileum demonstrated that l-HCZ is significantly more potent than d- and racemic HCZ. The pharmacokinetics of d- and l-HCZ after oral administration to rats also differed. The successful resolution of racemic HCZ permits comparison of the pharmacokinetics and antihistamine activity of the enantiomers.
Nishikata
M
M
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Nakai
A
A
Fushida
H
H
Miyake
K
K
Arita
T
T
Kitagawa
S
S
Kunitomo
M
M
Iseki
K
K
Miyazaki
K
K
D000818:Animals; D003501:Cyclizine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009904:Optical Rotation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D006634:Histamine H1 Antagonists; C034022:homochlorocyclizine; D003501:Cyclizine