Login I S, Cronin M J, Harcus C T, MacLeod R M
Proc Soc Exp Biol Med. 1983 Feb;172(2):225-31. doi: 10.3181/00379727-172-41550.
Tetrabenazine is considered to be a reserpine-like drug because of its ability to block dopamine storage in presynaptic vesicles. We used two methods to determine that tetrabenazine is also a dopamine antagonist. Tetrabenazine displaced the specific [3H]spiperone binding to the dopamine receptors of the anterior pituitary, the corpus striatum, and a transplantable rat pituitary tumor with values for 50% displacement (IC50) of about 15 microM. Under in vitro conditions, 0.5 to 10 microM tetrabenazine blocked dopaminergic inhibition of prolactin secretion from rat anterior pituitary glands. One, four, and twenty-four hours after a single tetrabenazine injection (30 mg/kg, ip), the serum prolactin changed from 22 +/- 9 ng/ml initially, to 450 +/- 52, 254.7 +/- 10.4, and 9.3 +/- 1.1 ng/ml, respectively. Pituitary glands of the treated rats incubated in vitro were refractory to dopaminergic inhibition of prolactin release to an extent that was maximal at one hour but inapparent by 24 hours after injection. In vivo and in vitro, tetrabenazine induces biological responses characteristic of a dopamine antagonist. These actions are independent of the reserpine-like properties of tetrabenazine. The unusual ability of tetrabenazine both to antagonize dopamine and to block presynaptic dopamine storage may provide a new tool for understanding the physiology of dopaminergic systems.
丁苯那嗪被认为是一种类似于利血平的药物，因为它能够阻断多巴胺在突触前囊泡中的储存。我们使用了两种方法来确定丁苯那嗪也是一种多巴胺拮抗剂。丁苯那嗪能取代特异性的[3H]司来吉兰与垂体前叶、纹状体和一种可移植大鼠垂体肿瘤的多巴胺受体结合，其50%取代值（IC50）约为15微摩尔。在体外条件下，0.5至10微摩尔的丁苯那嗪可阻断多巴胺对大鼠垂体前叶催乳素分泌的抑制作用。单次注射丁苯那嗪（30毫克/千克，腹腔注射）后1小时、4小时和24小时，血清催乳素分别从最初的22±9纳克/毫升变为450±52、254.7±10.4和9.3±1.1纳克/毫升。体外培养的经处理大鼠的垂体对多巴胺对催乳素释放的抑制作用具有抗性，这种抗性在注射后1小时达到最大，但在24小时后不明显。在体内和体外，丁苯那嗪均可诱导出多巴胺拮抗剂的生物学反应。这些作用与丁苯那嗪类似利血平的特性无关。丁苯那嗪既能拮抗多巴胺又能阻断突触前多巴胺储存的独特能力，可能为理解多巴胺能系统的生理学提供一种新工具。
