Schmiechen R, Schneider H H, Wachtel H
Research Laboratories of Schering AG, Department of Neuropsychopharmacology, Berlin.
Psychopharmacology (Berl). 1990;102(1):17-20. doi: 10.1007/BF02245738.
The antidepressant rolipram interacts in vitro with a binding site in brain tissue labeled by 3H-rolipram. A 3H-rolipram binding assay was employed in vivo to compare the affinity of rolipram-related compounds and reference phosphodiesterase (PDE) inhibitors with their potency in behavioural measures for potential antidepressant property. In two species, mice and rats, the potency of a number of compounds to antagonise reserpine-induced hypothermia (mice) and to induce head twitches (rats) was determined, as well as their potency to displace 3H-rolipram from forebrain binding sites in vivo. The treatment schedules for the two series of experiments were identical. Significant correlations between pharmacological effects and displacement of 3H-rolipram binding in vivo were observed in both species. Since the reference PDE inhibitors closely fit into the binding-pharmacological activity relationship, the PDE inhibitory properties of the substances involved are discussed.
抗抑郁药咯利普兰在体外与脑组织中由³H-咯利普兰标记的结合位点相互作用。采用³H-咯利普兰结合试验在体内比较咯利普兰相关化合物和参考磷酸二酯酶（PDE）抑制剂的亲和力与其在行为测量中潜在抗抑郁特性的效力。在小鼠和大鼠这两个物种中，测定了多种化合物拮抗利血平诱导的体温过低（小鼠）和诱发头部抽搐（大鼠）的效力，以及它们在体内从前脑结合位点置换³H-咯利普兰的效力。这两个系列实验的治疗方案相同。在两个物种中均观察到体内药理效应与³H-咯利普兰结合置换之间存在显著相关性。由于参考PDE抑制剂与结合-药理活性关系密切契合，因此对所涉及物质的PDE抑制特性进行了讨论。
