France C P, Winger G, Medzihradsky F, Seggel M R, Rice K C, Woods J H
Department of Pharmacology, University of Michigan, Ann Arbor.
J Pharmacol Exp Ther. 1991 Aug;258(2):502-10.
Mirfentanil [N-(2-pyrazinyl)-N-(1-phenethyl-4-piperidinyl)-2-furamide] was studied for its binding affinity in isolated neuronal membranes, and for its effects in vivo. In binding to opioid receptors in monkey brain membranes, mirfentanil was much more selective for mu sites (7.99 nM) than for either kappa (1428 nM) or delta (480 nM) sites as measured by displacement of [3H]DAMGO. [3H]U-69.593 or [3H]DPDPE, respectively. In morphine-treated pigeons discriminating among naltrexone, saline and morphine, mirfentanil failed to substitute for either training drug; in morphine-abstinent pigeons, mirfentanil reversed responding on the naltrexone key (i.e., reversed withdrawal). In morphine-treated monkeys discriminating between saline and naltrexone, mirfentanil substituted completely for naltrexone, and this effect was attenuated by an acute injection of morphine; mirfentanil also attenuated the withdrawal-reversing effects of alfentanil in morphine-abstinent monkeys. Administered i.v., mirfentanil maintained rates of self-administration responding only slightly below rates maintained by alfentanil, and this effect of mirfentanil was antagonized by quadazocine. Small doses of mirfentanil (0.032-0.32 mg/kg) antagonized the analgesic effects of alfentanil; larger doses of mirfentanil both antagonized the analgesic effects of alfentanil and produced analgesic effects when administered alone. The analgesic effects of mirfentanil were not attenuated by large doses of opioid antagonists. Mirfentanil had modest respiratory depressant effects that were not altered by quadazocine; however, mirfentanil antagonized the respiratory depressant effects of large doses of alfentanil. Both in vivo and in vitro, mirfentanil appears to have selectivity for opioid mu receptors. Moreover, at doses larger than those which exert opioid effects, mirfentanil has nonopioid analgesic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
米芬太尼[N-(2-吡嗪基)-N-(1-苯乙基-4-哌啶基)-2-呋喃甲酰胺]在离体神经元膜中的结合亲和力及其体内效应得到了研究。在与猴脑膜中的阿片受体结合时，通过[3H]DAMGO、[3H]U-69.593或[3H]DPDPE的置换测定，米芬太尼对μ位点（7.99 nM）的选择性远高于κ位点（1428 nM）或δ位点（480 nM）。在对纳曲酮、生理盐水和吗啡进行区分的吗啡处理鸽子中，米芬太尼无法替代任何一种训练药物；在吗啡戒断的鸽子中，米芬太尼使对纳曲酮键的反应逆转（即逆转戒断反应）。在区分生理盐水和纳曲酮的吗啡处理猴子中，米芬太尼完全替代了纳曲酮，且这种效应被急性注射吗啡减弱；米芬太尼还减弱了阿芬太尼对吗啡戒断猴子的戒断逆转效应。静脉注射时,米芬太尼维持自我给药反应速率仅略低于阿芬太尼维持的速率，且米芬太尼这种效应被夸达佐辛拮抗。小剂量米芬太尼（0.032 - 0.32 mg/kg）拮抗阿芬太尼的镇痛作用；大剂量米芬太尼既拮抗阿芬太尼的镇痛作用又单独给药时产生镇痛作用。米芬太尼的镇痛作用不被大剂量阿片拮抗剂减弱。米芬太尼有适度的呼吸抑制作用，且不被夸达佐辛改变；然而，米芬太尼拮抗大剂量阿芬太尼的呼吸抑制作用。无论在体内还是体外，米芬太尼似乎对阿片μ受体具有选择性。此外，在高于发挥阿片样作用剂量时，米芬太尼具有非阿片类镇痛作用。（摘要截短于250字）
