Portoles A, Ojeda G, Portoles M P, Rojo J M
Int J Tissue React. 1982;4(2):133-40.
The effects of chlorpromazine, haloperidol, clozapine and clotiapine on the mitogenic activation of spleen and bone-marrow cells were investigated. The use of two types of treatments (in vitro with 1.5 to 3 x 10(-3) mM for three days and in vivo with 0.3 mM for four days) permitted the demonstration that chlorpromazine was the most effective drug to inhibit DNA synthesis in mitogen stimulated mouse spleen cell cultures. However, in more prolonged in vivo treatments with a lower dose (0.075 mM for two weeks), clozapine and clotiapine frequently appeared as the most active inhibitors of mitogen-induced lymphoblastic transformation. In any case splenic T lymphocytes were more affected than B cells of the same origin. (3H) TdR uptake in DXS-stimulated bone-marrow cell cultures was also variably inhibited by in vivo drug treatments of mice as compared to groups of untreated animals. Occasionally, the effect of the drugs in vivo depend on the length of the treatment, rather than the dose administered. All these inhibitory effects did not appear as a phenomenon of cytotoxicity since doses used in vitro inhibit by less than 5% the cell viability. It is suggested that the variable depressions of the different mitogenic responses, produced by these neuroleptic drugs, may reflect an alteration in the cyclic AMP levels as a consequence of its inhibition of a phosphodiesterase activator.
研究了氯丙嗪、氟哌啶醇、氯氮平和氯噻平对脾细胞和骨髓细胞有丝分裂原激活的影响。采用两种处理方式（体外1.5至3×10⁻³ mM处理三天，体内0.3 mM处理四天），结果表明氯丙嗪是抑制有丝分裂原刺激的小鼠脾细胞培养物中DNA合成最有效的药物。然而，在更低剂量（0.075 mM，持续两周）的更长时间体内处理中，氯氮平和氯噻平常常表现为有丝分裂原诱导的淋巴细胞转化的最有效抑制剂。无论如何，脾T淋巴细胞比同源的B细胞受影响更大。与未处理动物组相比，小鼠体内药物处理也不同程度地抑制了DXS刺激的骨髓细胞培养物中（³H）TdR的摄取。偶尔，药物在体内的作用取决于处理时间，而非给药剂量。所有这些抑制作用并非细胞毒性现象，因为体外使用的剂量对细胞活力的抑制小于5%。有人提出，这些抗精神病药物对不同有丝分裂反应的不同程度抑制，可能反映了由于其对磷酸二酯酶激活剂的抑制而导致的环磷酸腺苷水平的改变。
