al-Rodhan N R, Yaksh T L, Kelly P J
Department of Neurosurgery, Mayo Clinic, Rochester, Minn.
Stereotact Funct Neurosurg. 1992;59(1-4):15-9. doi: 10.1159/000098910.
SCH-32615 is a new enkephalinase inhibitor whose analgesic effects were examined following its stereotactic microinjection into the periaqueductal gray (PAG) and the ventromedial medulla (VMM) regions of the brainstem of the rat. SCH-32615 produced a strong, dose-dependent, naloxone-reversible analgesia to thermal noxious stimuli as measured by the hot plate test (HP; supraspinal analgesia) and the tail flick test (TF; spinal analgesia). The peak analgesic effect was seen within 10 min and remained for 45-60 min. ED50 were for PAG, HP = 10.7 micrograms and TF = 17.3 micrograms, and for VMM, HP = 5.7 micrograms and TF = 7.2 micrograms. Using the irreversible mu receptor antagonist, beta-funaltrexamine, it was found that the endogenous enkephalins in the PAG produce their analgesic effects by acting at only one receptor subtype (the mu receptor) while in the VMM both mu and delta opioid receptors are involved (not through the delta alone as previously believed).
SCH-32615是一种新型脑啡肽酶抑制剂，在将其立体定向微量注射到大鼠脑干的导水管周围灰质（PAG）和延髓腹内侧（VMM）区域后，对其镇痛作用进行了研究。通过热板试验（HP；脊髓上镇痛）和甩尾试验（TF；脊髓镇痛）测定，SCH-32615对热伤害性刺激产生了强烈的、剂量依赖性的、纳洛酮可逆的镇痛作用。镇痛作用在10分钟内达到峰值，并持续45-60分钟。PAG的半数有效剂量（ED50）为：HP = 10.7微克，TF = 17.3微克；VMM的ED50为：HP = 5.7微克，TF = 7.2微克。使用不可逆的μ受体拮抗剂β-氟奈曲胺发现，PAG中的内源性脑啡肽仅通过作用于一种受体亚型（μ受体）产生镇痛作用，而在VMM中，μ和δ阿片受体均参与其中（并非如先前认为的仅通过δ受体）。
