語系:
繁體中文
English
說明(常見問題)
回圖書館首頁
手機版館藏查詢
登入
回首頁
切換:
標籤
|
MARC模式
|
ISBD
Gamma-hydroxybutyric acid tolerance ...
~
Raybon, Joseph Jackson.
FindBook
Google Book
Amazon
博客來
Gamma-hydroxybutyric acid tolerance development: Pharmacokinetic and pharmacodynamic perspectives.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Gamma-hydroxybutyric acid tolerance development: Pharmacokinetic and pharmacodynamic perspectives./
作者:
Raybon, Joseph Jackson.
面頁冊數:
255 p.
附註:
Adviser: Kathleen M. K. Boje.
Contained By:
Dissertation Abstracts International67-11B.
標題:
Health Sciences, Pharmacology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3244205
ISBN:
9780542997907
Gamma-hydroxybutyric acid tolerance development: Pharmacokinetic and pharmacodynamic perspectives.
Raybon, Joseph Jackson.
Gamma-hydroxybutyric acid tolerance development: Pharmacokinetic and pharmacodynamic perspectives.
- 255 p.
Adviser: Kathleen M. K. Boje.
Thesis (Ph.D.)--State University of New York at Buffalo, 2006.
Gamma-hydroxybutyric acid (GHB) is a central nervous system depressant and drug of abuse. Chronic exposure results in the development of tolerance to its sedative/hypnotic effects. For centrally-acting substances, the existence of tolerance may be a strong indicator of drug dependence and thus a good predictor of a drug's abuse liability. The goal of this dissertation was to investigate the roles of pharmacokinetics (PK) and pharmacodynamics (PD) in the development and expression of GHB tolerance. Various in vitro and in vivo studies were performed to attain a better understanding of this phenomenon. Following five days of GHB administration in rats (548 mg/kg s.c., once daily), the sedative/hypnotic effect time was significantly decreased as a function of days of exposure. We hypothesized that this behavioral change could be mediated, in part, through alterations in neuronal membrane fluidity. Using fluorescence polarization studies, GHB sedative tolerance was found to be associated with a decrease in the membrane fluidity of neuronal preparations which was not due to a direct drug-membrane interaction. Further explorations in vitro revealed that an increase in the neuronal re-uptake of GABA, a mediator of GHB's inhibitory effects, also accompanies the observed biophysical and behavioral changes. In contrast to biophysical or neurochemical changes, an alternative hypothesis that would explain the observed decrease in GHB's sedative effects might involve changes in the pharmacokinetics. It was shown that, upon multiple dosing (548 mg/kg s.c., once daily for 5 days), the behavioral tolerance towards GHB was not associated with alterations in the either the systemic or CNS pharmacokinetics, as probed by microdialysis. However, pharmacodynamic tolerance did develop towards GHB's inhibition of extracellular dopamine release and, as indicated by PKPD modeling, it is likely the result of decreased sensitivity towards GHB's depressant effects. In conclusion it appears that the development of GHB tolerance is multi-faceted, involving biophysical adaptations, changes in neuronal regulatory processes and neurochemical responsiveness, all of which may or may not be related to one another.
ISBN: 9780542997907Subjects--Topical Terms:
1017717
Health Sciences, Pharmacology.
Gamma-hydroxybutyric acid tolerance development: Pharmacokinetic and pharmacodynamic perspectives.
LDR
:03144nam 2200277 a 45
001
958510
005
20110704
008
110704s2006 eng d
020
$a
9780542997907
035
$a
(UMI)AAI3244205
035
$a
AAI3244205
040
$a
UMI
$c
UMI
100
1
$a
Raybon, Joseph Jackson.
$3
1281971
245
1 0
$a
Gamma-hydroxybutyric acid tolerance development: Pharmacokinetic and pharmacodynamic perspectives.
300
$a
255 p.
500
$a
Adviser: Kathleen M. K. Boje.
500
$a
Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6333.
502
$a
Thesis (Ph.D.)--State University of New York at Buffalo, 2006.
520
$a
Gamma-hydroxybutyric acid (GHB) is a central nervous system depressant and drug of abuse. Chronic exposure results in the development of tolerance to its sedative/hypnotic effects. For centrally-acting substances, the existence of tolerance may be a strong indicator of drug dependence and thus a good predictor of a drug's abuse liability. The goal of this dissertation was to investigate the roles of pharmacokinetics (PK) and pharmacodynamics (PD) in the development and expression of GHB tolerance. Various in vitro and in vivo studies were performed to attain a better understanding of this phenomenon. Following five days of GHB administration in rats (548 mg/kg s.c., once daily), the sedative/hypnotic effect time was significantly decreased as a function of days of exposure. We hypothesized that this behavioral change could be mediated, in part, through alterations in neuronal membrane fluidity. Using fluorescence polarization studies, GHB sedative tolerance was found to be associated with a decrease in the membrane fluidity of neuronal preparations which was not due to a direct drug-membrane interaction. Further explorations in vitro revealed that an increase in the neuronal re-uptake of GABA, a mediator of GHB's inhibitory effects, also accompanies the observed biophysical and behavioral changes. In contrast to biophysical or neurochemical changes, an alternative hypothesis that would explain the observed decrease in GHB's sedative effects might involve changes in the pharmacokinetics. It was shown that, upon multiple dosing (548 mg/kg s.c., once daily for 5 days), the behavioral tolerance towards GHB was not associated with alterations in the either the systemic or CNS pharmacokinetics, as probed by microdialysis. However, pharmacodynamic tolerance did develop towards GHB's inhibition of extracellular dopamine release and, as indicated by PKPD modeling, it is likely the result of decreased sensitivity towards GHB's depressant effects. In conclusion it appears that the development of GHB tolerance is multi-faceted, involving biophysical adaptations, changes in neuronal regulatory processes and neurochemical responsiveness, all of which may or may not be related to one another.
590
$a
School code: 0656.
650
4
$a
Health Sciences, Pharmacology.
$3
1017717
650
4
$a
Health Sciences, Pharmacy.
$3
1017737
690
$a
0419
690
$a
0572
710
2 0
$a
State University of New York at Buffalo.
$3
1017814
773
0
$t
Dissertation Abstracts International
$g
67-11B.
790
$a
0656
790
1 0
$a
Boje, Kathleen M. K.,
$e
advisor
791
$a
Ph.D.
792
$a
2006
856
4 0
$u
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3244205
筆 0 讀者評論
館藏地:
全部
電子資源
出版年:
卷號:
館藏
1 筆 • 頁數 1 •
1
條碼號
典藏地名稱
館藏流通類別
資料類型
索書號
使用類型
借閱狀態
預約狀態
備註欄
附件
W9121975
電子資源
11.線上閱覽_V
電子書
EB W9121975
一般使用(Normal)
在架
0
1 筆 • 頁數 1 •
1
多媒體
評論
新增評論
分享你的心得
Export
取書館
處理中
...
變更密碼
登入