κ-類鴉片受體於鴉片類藥物的依賴性所扮演的角色   全文下載

The κ-Opioid Receptor in Opioid Dependence

依賴性目前仍是臨床使用作用於μ-類鴉片受體的鎮痛劑所主要關切的問題，因此使用κ-類鴉片受體的藥物以取代μ-受體致效劑作為鎮痛劑的情形正逐漸成長中。有些研究報告指出慢性給予κ-鴉片受體致效劑，如U-50488H，U-69,593及butorphanol也能導致身體依賴性／脫癮症狀的產生，而不論由全身或由脊髓給予nor-binaltorphimine（一種高選擇性的κ-類鴉片受體拮抗劑）均可在依賴性的動物引起催癮現象，更顯示不論在腦或脊髓的κ-鴉片受體均在類鴉片藥物的依賴性／脫癮症狀上扮演了重要的角色。此外位於藍斑核（locus coeruleus）節前神經末端的κ-鴉片受體調控麩氨酸（glutamate）的釋放，可能與依賴性／脫癮症狀的表現有關。對κ-鴉片致效劑的身體依賴性與脊髓及特殊腦區κ類鴉片受體之減量和對拮抗劑敏感的狀態有關；然而κ-類鴉片受體的改變可能無法完全解釋依賴性發生的機轉。由最近κ-類鴉片受體的選殖（clone）成功及應用，未來應該能闡明其在依賴性／脫癮發生的細胞生物機轉上與μ-類鴉片受體可能不同。"

Opioid dependence that particularly mediates through the µ-opioid receptor remains a major concern of opioid analgesics. Drugs which interact with κ-opioid receptors are increasingly used as an alternative to µ-agonist analgesic. Several studies have reported that chronic administration of κ-opioid agonists such as U-504880, U-69,593, and butorphanol also results in development of physical dependence/withdrawal. In addition, the ability of a highly selective κ-opioid antagonist, nor-binaltorphimine, given systemically or spinally, to precipitate withdrawal behaviors in opioid-dependent animals further demonstrates that both supraspinal and spinal sites of κ-opioid receptors play an important role in opioid dependence/withdrawal. With regard to the role of glutamate in opioid dependence/withdrawal, theκ-opioid receptor located at the presynaptic nerve terminal within the locus coeruleus crucially regulates glutamate release during the expression of opioid withdrawal. Physical dependence on κ-opioid agonists is associated with the downregulation and antagonist-sensitive state of the κ-opioid receptor in the spinal cord and specific brain areas. However, alterations of the κ-opioid receptor may not completely explain the mechanisms of dependence development. With cloned κ-opioid receptors recently available, it could be elucidated that the cellular and biological mechanisms of κ-opioid receptors for the development of dependence/withdrawal may differ from those of µ-opioid receptors. 依賴性目前仍是臨床使用作用於μ-類鴉片受體的鎮痛劑所主要關切的問題，因此使用κ-類鴉片受體的藥物以取代μ-受體致效劑作為鎮痛劑的情形正逐漸成長中。有些研究報告指出慢性給予κ-鴉片受體致效劑，如U-50488H，U-69,593及butorphanol也能導致身體依賴性／脫癮症狀的產生，而不論由全身或由脊髓給予nor-binaltorphimine（一種高選擇性的κ-類鴉片受體拮抗劑）均可在依賴性的動物引起催癮現象，更顯示不論在腦或脊髓的κ-鴉片受體均在類鴉片藥物的依賴性／脫癮症狀上扮演了重要的角色。此外位於藍斑核（locus coeruleus）節前神經末端的κ-鴉片受體調控麩氨酸（glutamate）的釋放，可能與依賴性／脫癮症狀的表現有關。對κ-鴉片致效劑的身體依賴性與脊髓及特殊腦區κ類鴉片受體之減量和對拮抗劑敏感的狀態有關；然而κ-類鴉片受體的改變可能無法完全解釋依賴性發生的機轉。由最近κ-類鴉片受體的選殖（clone）成功及應用，未來應該能闡明其在依賴性／脫癮發生的細胞生物機轉上與μ-類鴉片受體可能不同。