Horowski R, Gräf K J
Arch Toxicol Suppl. 1979(2):93-104. doi: 10.1007/978-3-642-67265-1_7.
As an example for the importance of the neuroendocrine system in the toxicological evaluation of neuropsychotropic drugs, the influence of functional dopaminergic agonists and antagonists on the secretion of prolactin is studied. In rats, all functional dopamine antagonists (reserpine alone or combined with alpha-methyl-p-tyrosine or benserazide, haloperidol, spiroperidol, sulpiride) increased serum PRL levels. Dopaminergic agonists (apomorphine, piribedil, d-amphetamine, L-DOPA, and the ergot derivatives bromocriptine and lisuride) all caused a decrease of serum prolactin levels. The same effect could be observed also after treatment with other ergot derivatives such as d-LSD, methergoline, methysergide and ergotamine. Also in this case, the prolactin-lowering effect seems to be related to dopaminergic activity. This was suggested by the inhibitory effect of pretreatment with the dopamine antagonist spiroperidol or with sulpiride on the prolactin-lowering effect of lisuride. In dogs, thyrotropin releasing hormone (TRH) increased and lisuride decreased serum prolactin levels determined with a new radioimmunoassay. As an example for the situation in humans, the effects of the dopamine antagonist sulpiride and of the dopamine agonist bromocriptine were described. The prolactin levels were higher in the presence of estrogens. The relevance of these neuroendocrine effects of neuropsychotropic drugs on physiological systmes in animals and man is discussed.
作为神经内分泌系统在神经精神药物毒理学评估中的重要性的一个例子，研究了功能性多巴胺能激动剂和拮抗剂对催乳素分泌的影响。在大鼠中，所有功能性多巴胺拮抗剂（单独使用利血平或与α-甲基-对-酪氨酸或苄丝肼联合使用、氟哌啶醇、螺哌啶醇、舒必利）均提高了血清催乳素水平。多巴胺能激动剂（阿扑吗啡、匹莫齐特、右旋苯丙胺、左旋多巴以及麦角衍生物溴隐亭和利舒脲）均导致血清催乳素水平降低。在用其他麦角衍生物如d-麦角酸二乙胺、美替拉酮、甲基麦角新碱和麦角胺治疗后也可观察到相同的效果。同样在这种情况下，催乳素降低作用似乎与多巴胺能活性有关。多巴胺拮抗剂螺哌啶醇或舒必利预处理对利舒脲的催乳素降低作用的抑制效应表明了这一点。在犬中，促甲状腺激素释放激素（TRH）提高了血清催乳素水平，而利舒脲则降低了用一种新的放射免疫测定法测定的血清催乳素水平。作为人类情况的一个例子，描述了多巴胺拮抗剂舒必利和多巴胺激动剂溴隐亭的作用。在有雌激素存在时催乳素水平较高。讨论了神经精神药物的这些神经内分泌效应与动物和人类生理系统的相关性。
