類鴉片受體與Butorphanol藥物依賴性   全文下載

Opioid Receptors and Butorphanol Dependence

Butorphanol是一種兼具有催動和拮抗類鴉片受體之藥物，常Butorphanol使用劑量在治療範圍內時係屬於一種較安全的藥劑。然而，各種不同的使用量，甚至高劑量的使用亦巳經被報導。本研究係探討在Butorphanol生理依賴性的灰鼠中μ,δ,和κ類鴉片受體相對參與程度。藉著對雄性Sprague-Dawley灰鼠腦室連續注射Butorphanol （26 nmol／h）達72小時，可使灰鼠對Butorphanol產生生理的依賴性。然而，若對灰鼠腦室分別注射不同劑量的β-funaltrexamine （β-FNA，一種μ類鴉片受體拮抗劑，注射量分別為12、24、或48 nmo1／5 μm）、naltrindole（NTI，一種δ類鴉片受體拮抗劑，注射量分別為0.1、1或10 nmo1／5μl）或nor-binaltorphimine（nor-BN1，一種κ類鴉片受體拮抗劑，注射量分別為12、24或48 nmo1／5μl）將顯著減緩灰鼠對butorphanol生理依賴性的產生。此外，若同時對灰鼠腦室注射不同劑量的NTI（24、48或100 nmol／5μl）和nor-BNI（3、10、20、48或100 nmol／5μl）將迅速促使ˇ斷癮徵狀發生，然而，若投與β-FNA （12、24、48或100 nmol／5μl）則無法促使butorphanol生理依賴性的灰鼠產生斷癮徵狀。本結果顯示butorphanol生理依賴性的產生係butorphanol影響到腦部μ,δ,和κ類鴉片受體所導致。"

Butorphanol, a mixed opioid agonist/antagonist, is considered to be a relatively safe drug when used within the therapeutic dose range. However, diversional uses of butorphanol involving high doses have been documented. In the present review, the relative involvement of µ-, δ-, and κ-opioid receptors in butorphanol physical dependence in rats is discussed. Physical dependence was produced by continuous intracerebroventricular (icv) infusion of butorphanol (26 nmol/h) for 72 h in male Sprague-Dawley rats. Multiple icv injections of β-funaltrexaimne (β-FNA, a µ-antagonist, 12, 24, or 48 nmol/5 µl), naltrindole (NTI, δ-antagonist, 0.1, 1, or 10 nmol/5 µl), or nor-binaltorphimine (nor-BNI, a κ-antagonist, 12, 24, or 48 nmol/5 µl) significantly attenuated the development of butorphanol dependence. Furthermore, icv administration of both NTI (24, 48, or 100 nmol/5 µl) and nor-BNI (3, 10, 20, 48, or 100 nmol/5 µl) precipitated withdrawal behaviors, whereas, β-FNA (12, 24, 48, or 100 nmol/5 µl) was unable to elicit withdrawal signs in butorphanol-dependent rats. The results indicate that the development of butorphanol dependence is due to effects of butorphanol on central µ-, 8-, and κ-opioid receptors.