Waszczak B L, Hruska R E, Walters J R
Eur J Pharmacol. 1980 Jul 11;65(1):21-9. doi: 10.1016/0014-2999(80)90204-6.
GABAmimetic actions of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol (THIP) were evaluated both in vivo and in vitro and compared with the actions of muscimol and GABA. The GABAergic potencies of these agents were assessed in vivo by measuring their ability to inhibit firing of rat substantia nigra pars reticulata neurons after systemic administration and iontophoretic applications, and in vitro by measuring their ability to inhibit 3H-GABA binding to rat cerebellar membranes. The effects of THIP were found to be similar to those of muscimol and GABA with regard to inhibition of reticulata cell firing and 3H-GABA binding. The order of potency was muscimol > GABA > THIP. The magnitude of the differences between drug potencies in iontophoretic studies closely paralleled their relative potencies in binding studies, with muscimol approximately 3 times more potent than GABA and 25-40 times more potent than THIP. After systemic (i.v.) administration, however, muscimol was only 3 times more potent than THIP in inhibiting reticulata cell firing, possibly because THIP passes the blood-brain barrier more readily.
对4,5,6,7-四氢异恶唑并-[5,4-c]-吡啶-3-醇（THIP）的拟GABA作用进行了体内和体外评估，并与蝇蕈醇和GABA的作用进行了比较。通过测量全身给药和离子导入应用后它们抑制大鼠黑质网状部神经元放电的能力，在体内评估这些药物的GABA能效力；通过测量它们抑制3H-GABA与大鼠小脑膜结合的能力，在体外评估其效力。就抑制网状部细胞放电和3H-GABA结合而言，发现THIP的作用与蝇蕈醇和GABA的作用相似。效力顺序为蝇蕈醇>GABA>THIP。离子导入研究中药物效力之间差异的大小与其在结合研究中的相对效力密切平行，蝇蕈醇的效力约为GABA的3倍，是THIP的25 - 40倍。然而，全身（静脉）给药后，蝇蕈醇在抑制网状部细胞放电方面仅比THIP强3倍，这可能是因为THIP更容易通过血脑屏障。
