Abstract: AIM: To study the distribution of penehyclidine hydrochloride (PHC) raceme and its four optical isomers in mice and the effects of QNB on distribution of PHC.METHODS: The tissue concentrations of PHC raceme and its four optical isomers in mice were determined by gas chromatography-mass spectrometry with selected ion monitoring (GC-MS/SIM) PHC (m/z 175) and PHC-5 (m/z 180) as internal standard.RESULTS: The main pharmacokinetic parameters of PHC raceme in mice brain after im a single dose (0.1 mg·kg^-1) were as follows: T_1/2β = 35.16±5.4 h, C_max = 66.98±12.6 ng·g^-1, and AUC = 2.1±0.4 μg·h^-1·g^-1. The distribution concentrations in brain had a significantly persistent level for more than 48 h. PHC raceme and the four optical isomers were high selectively distributed in mice brain. The results showed that the concentration of distribution of R-2 isomer had a higher level. And the isomer with S-configuration in mice brain eliminated fast and isomer with R-configuration eliminated slowly. And the tissue concentration of R-2 isomer had a high level which R-2 isomer had a great affinity with mAChR.The distribution concentration of the four optical isomers in mice brain obviously decreased after or before QNB was given. Among them, the R-2 isomer was influenced more greatly by QNB, which R-2 had the highest biological potency. It suggested that the distribution of R-2 isomer in mice brain was mainly related to mAChR.CONCLUSION: There is a relationship between the tissue concentration of the isomer in mice brain and the affinity of the isomer to mAChR. QNB can affect the distribution of PHC and its four isomers in mice brain.

Key words: penhyclidine hydrochloride, optical isomers, QNB, distribution, GC-MS/SIM