Liptrot J, Holdup D, Phillipson O
Department of Anatomy, School of Medical Sciences, University of Bristol, United Kingdom.
J Neural Transm Gen Sect. 1994;96(1):51-62. doi: 10.1007/BF01277928.
1,2,3,4-tetrahydro-2-methyl-4,6,7-isoquinolinetriol (TMIQ), a tetrahydroisoquinoline derivative of adrenaline, was tested for potency as an analog of the dopamine depleting agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in assays of tyrosine hydroxylase (TH) activity in the striatal synaptosome preparation. TMIQ inhibited TH activity with an IC50 (4 x 10(-6)M) similar to that found for MPTP (IC50 1 x 10(-6)M). TH inhibitions produced by IC50 concentrations of TMIQ were reversed by monoamine oxidase (MAO)-A or MAO-B inhibitors (clorgyline or deprenyl), or the dopamine reuptake blocker nomifensine, or excess cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin. TMIQ did not appear to act at the presynaptic D2 sulpiride sensitive autoreceptor for dopamine synthesis modulation. These in vitro data are consistent with earlier findings that TMIQ acts as a dopamine depleting agent, and with the possibility that TMIQ may have a degree of MPTP-like activity in vivo.
1,2,3,4-四氢-2-甲基-4,6,7-异喹啉三醇（TMIQ）是肾上腺素的一种四氢异喹啉衍生物，在纹状体突触体制剂中酪氨酸羟化酶（TH）活性测定中，作为多巴胺耗竭剂1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的类似物进行了效能测试。TMIQ抑制TH活性的IC50（4×10⁻⁶M）与MPTP的IC50（1×10⁻⁶M）相似。IC50浓度的TMIQ所产生的TH抑制作用可被单胺氧化酶（MAO）-A或MAO-B抑制剂（氯吉兰或司来吉兰）、多巴胺再摄取阻滞剂诺米芬辛或过量辅因子（6R）-5,6,7,8-四氢-L-生物蝶呤逆转。TMIQ似乎并不作用于用于多巴胺合成调节的突触前D2舒必利敏感自受体。这些体外数据与早期发现一致，即TMIQ作为一种多巴胺耗竭剂起作用，并且与TMIQ在体内可能具有一定程度的MPTP样活性的可能性一致。
