期刊
PHARMACEUTICAL RESEARCH
卷 30, 期 9, 页码 2368-2384出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-013-1080-x
关键词
antipsychotics; catalepsy; central nervous system; intranasal administration; metabolism
资金
- CUHK Direct Grant [4450272]
- General Research Fund CUHK [480809]
To elucidate the role of metabolism in the pharmacokinetics and pharmacodynamics of intranasal loxapine in conscious animals. At pre-determined time points after intranasal or oral loxapine administration, levels of loxapine, loxapine metabolites, and neurotransmitters in rat brain were quantified after catalepsy assessments (block test and paw test). Cataleptogenicity of loxapine was also compared with its metabolites. Intranasally administered loxapine was efficiently absorbed into systemic circulation followed by entering brain, with t(max) a parts per thousand currency sign15 min in all brain regions. Oral route delivered minimal amounts of loxapine to plasma and brain. Brain AUC(0-240min) values of 7-hydroxy-loxapine were similar after intranasal and oral administration. Intranasal loxapine tended to induce less catalepsy than oral loxapine, although statistical significance was not reached. The catalepsy score was positively and significantly correlated with the striatal concentration of 7-hydroxy-loxapine, but not with loxapine. 7-hydroxy-loxapine was more cataleptogenic than loxapine, while the presence of loxapine tended to reduce rather than intensify 7-hydroxy-loxapine-induced catalepsy. The increases in striatal dopamine turnover were comparable after intranasal and oral loxapine administration. The metabolite 7-hydroxy-loxapine, but not loxapine, was the main contributor to the catalepsy observed after intranasal and oral loxapine treatment. Intranasal route could effectively deliver loxapine to brain.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据