Grognet A, Hertz F, DeFeudis F V
Gen Pharmacol. 1983;14(6):585-9. doi: 10.1016/0306-3623(83)90153-2.
The antinociceptive actions of intraperitoneally-administered 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and morphine were compared using three strains of mice. With the hot-plate assay, ED50 values for the action of THIP were about 4 mg/kg in OF1, CD1 and NMRI strains, whereas ED50 values for morphine varied among strains, being 6.8 mg/kg for OF1, 16.9 mg/kg for CD1, and about 29 mg/kg for NMRI mice; thus, the genetic control of the analgesic action of THIP appears to differ from that of morphine. The analgesic action of THIP in the hot-plate test was not blocked by naloxone, bicuculline, phentolamine or methysergide, but was partially reversed by a high dose of atropine, indicating that classic opiate-receptors, bicuculline-sensitive GABA-receptors, alpha-adrenoceptors and serotonin-receptors do not appear to mediate the action of THIP but that cholinergic receptors might be indirectly involved. THIP was about equipotent or more potent than morphine in the phenylbenzoquinone writhing test, evasion test, and traction test. Since the ED50 values for THIP in OF1 mice were similar for hot-plate, evasion and traction tests, the analgesic action of THIP might not be readily dissociated from its sedative or myorelaxant action.
使用三种品系的小鼠比较了腹腔注射4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇（THIP）和吗啡的抗伤害感受作用。在热板试验中，THIP作用的半数有效量（ED50）在OF1、CD1和NMRI品系小鼠中约为4mg/kg，而吗啡的ED50值在不同品系间有所不同，OF1小鼠为6.8mg/kg，CD1小鼠为16.9mg/kg，NMRI小鼠约为29mg/kg；因此，THIP镇痛作用的遗传控制似乎与吗啡不同。热板试验中THIP的镇痛作用未被纳洛酮、荷包牡丹碱、酚妥拉明或甲基麦角新碱阻断，但可被高剂量阿托品部分逆转，这表明经典阿片受体、对荷包牡丹碱敏感的GABA受体、α-肾上腺素能受体和5-羟色胺受体似乎不介导THIP的作用，但胆碱能受体可能间接参与其中。在苯醌扭体试验、逃避试验和牵引试验中，THIP的效力约与吗啡相当或更强。由于OF1小鼠中THIP在热板试验、逃避试验和牵引试验中的ED50值相似，THIP的镇痛作用可能与其镇静或肌松作用不易区分。
