Opioid Receptors and Butorphanol Dependence

類鴉片受體與Butorphanol藥物依賴性

何英剛(Ing-Kang Ho) ； Shyhwen Jaw

《藥物食品分析》 3卷2期 (1995/07) Pp. 87-94

摘要

Butorphanol是一種兼具有催動和拮抗類鴉片受體之藥物，當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已經被報導。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-funaltrexaimne (β-FNA，一種μ類鴉片受體拮抗劑，注射量分別為12, 24，或48 nmol/5 μl)、naltrindole (NTI，一種δ類鴉片受體拮抗劑，注射量分別為0.1，1，或10 nmol/5 μl)或nor-binaltorphimine （nor-BNI, 一種κ類鴉片受體拮抗劑，注射量分別為12, 24或48 nmol/5 μl）將顯著減緩灰鼠對butorphanol生理依賴性的産生。此外，若同時對灰鼠腦室注射不同劑量的NTI（24, 48,或100 nmol/5 μl）和nor-BNI（3, 10, 20, 48,或100 nmol/5 μl）漿迅速促使斷癮徵狀發生，然而，若投與β-FNA（12, 24, 48或100 nmol/5 μl）則無法促使butorphanol生理依賴性的灰鼠産生斷癮徵狀。本結果顯示butorphanol生理依賴性的産生係butorphanol影響到腦部μ,δ,和κ類鴉片受體所導致。

關鍵字

Butorphanol ； β-Funaltrexaimne ； Naltrindole ； Nor-binaltorphimine ； 生理依賴性 ； μ,δ,和κ類鴉片受體

並列摘要

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 icy injections of β-funaltrexaimne (β-FNA, a μ-antagonist, 12, 24, or 48 nmol/5 μl), naltrindole (NTI, a 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, icy 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-, δ-, and κ-opioid receptors.

並列關鍵字

Butorphanol ； β-funaltrexamine ； naltrindole ； nor-binaltorphimine ； physical dependence ； μ- ； δ- ； and κ-opioid receptors