Bourde O, Schmitt P, Robert F, Richard F, Carbonnele A C, Thal C, Pujol J F
Laboratoire de Neuropharmacologie moléculaire, Faculté de Médecine A. Carrel, Lyon, France.
Neurochem Int. 1993 Dec;23(6):567-74. doi: 10.1016/0197-0186(93)90105-e.
RU24722, as a racemic mixture, has been found to act on neuronal activity and the long-term regulation of tyrosine hydroxylase in the locus coeruleus of the rat. In this study, the effects of two enantiomeric derivatives of RU24722 (3 alpha and 16 alpha forms), as compared to the racemic form itself, are studied. The short-term effect was estimated 20 min after treatment by measuring variations in 3,4-dihydroxyphenylacetic acid content in the locus coeruleus. The long-term effect was determined by evaluating tyrosine hydroxylase protein concentration in the locus coeruleus 3 days after a single injection. Comparison of actions of both enantiomers showed that the 16 alpha form was 3-fold more potent in eliciting tyrosine hydroxylase protein elevations at three days, whereas the 3 alpha isomer increased 3,4-dihydroxyphenylacetic acid content 2-fold more in the short-term. These results seem to show that the 16 alpha configuration is crucial for the long term regulation of tyrosine hydroxylase protein elicited by RU24722 within the locus coeruleus.
RU24722作为一种外消旋混合物，已被发现可作用于大鼠蓝斑中的神经元活动以及酪氨酸羟化酶的长期调节。在本研究中，研究了RU24722的两种对映体衍生物（3α和16α形式）与外消旋形式本身相比的作用。通过测量蓝斑中3,4-二羟基苯乙酸含量的变化来评估治疗后20分钟的短期效应。长期效应通过在单次注射3天后评估蓝斑中酪氨酸羟化酶蛋白浓度来确定。两种对映体作用的比较表明，16α形式在三天内引起酪氨酸羟化酶蛋白升高的效力是3倍，而3α异构体在短期内使3,4-二羟基苯乙酸含量增加2倍。这些结果似乎表明，16α构型对于RU24722在蓝斑内引起的酪氨酸羟化酶蛋白的长期调节至关重要。
