Hu J, Lee J H, el-Fakahany E E
Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Minneapolis 55455.
Psychopharmacology (Berl). 1994 Feb;114(1):161-6. doi: 10.1007/BF02245458.
There is rapidly accumulating evidence that generation of nitric oxide (NO) through a Ca2+ and calmodulin-dependent pathway plays various important roles in the central nervous system. In the present study, effects of several antipsychotics on the activity of NO synthase were investigated in rat cerebellum and neuroblastoma N1E-115 cells, due to the known ability of these agents to inhibit calmodulin. In cytosolic preparations of rat cerebellum, the antipsychotic drugs inhibited the conversion of [3H]L-arginine into [3H]L-citrulline by NO synthase in a concentration-dependent manner. This inhibition was noncompetitive in nature, and it exhibited an excellent correlation with blockade of calmodulin activity. Furthermore, these drugs attenuated cyclic GMP formation induced by a calcium ionophore in N1E-115 cells, a response which takes place as a consequence of NO generation. Taken together, our data demonstrate that antipsychotic drugs inhibit NO formation in vitro. It is unlikely, however, that these actions might contribute to their therapeutic and/or side effects, since they take place at relatively high concentrations.
越来越多的证据表明，通过钙和钙调蛋白依赖性途径生成一氧化氮（NO）在中枢神经系统中发挥着各种重要作用。在本研究中，由于已知这些药物能够抑制钙调蛋白，因此研究了几种抗精神病药物对大鼠小脑和神经母细胞瘤N1E - 115细胞中一氧化氮合酶活性的影响。在大鼠小脑的胞质制剂中，抗精神病药物以浓度依赖性方式抑制一氧化氮合酶将[3H]L - 精氨酸转化为[3H]L - 瓜氨酸。这种抑制本质上是非竞争性的，并且与钙调蛋白活性的阻断表现出极好的相关性。此外，这些药物减弱了钙离子载体在N1E - 115细胞中诱导的环鸟苷酸形成，这种反应是由NO生成引起的。综上所述，我们的数据表明抗精神病药物在体外抑制NO的形成。然而，这些作用不太可能导致它们的治疗和/或副作用，因为它们是在相对高的浓度下发生的。
