Anderson W R, Simpkins J W, Brewster M E, Bodor N
Pharmacol Biochem Behav. 1987 Jun;27(2):265-71. doi: 10.1016/0091-3057(87)90569-7.
We have developed a redox-chemical system for brain-enhanced drug delivery of estradiol based on an interconvertible dihydropyridine in equilibrium with pyridinium salt carrier. Estradiol, when combined with the carrier, readily crosses the blood-brain barrier and upon oxidation of the carrier is "locked" in the brain. The aim of this study was to evaluate the effects of an estradiol-chemical delivery system (E2-CDS) versus an equimolar dose of estradiol-17-valerate (E2-VAL) on copulatory behavior in orchidectomized rats. The data revealed that a single dose of E2-CDS was more efficacious than E2-VAL in stimulating mounting behavior (percent responding) and the effect was 100% through 5 weeks. E2-CDS increased intromission behavior more than E2-VAL through 28 days. Mount and intromission latencies were reduced by E2-CDS to a greater extent and for a longer time (28 days) than E2-VAL. Neither form of estradiol restored ejaculation parameters or penile reflexes. These data suggest that E2-CDS causes a potent and long-acting stimulation of proceptive and consummatory components of male sexual behavior, presumably acting through the local brain-release of estradiol.
我们基于与吡啶盐载体处于平衡状态的可相互转化的二氢吡啶，开发了一种用于脑增强雌二醇药物递送的氧化还原化学系统。雌二醇与载体结合后，能够轻易穿过血脑屏障，并且在载体氧化后“锁定”在大脑中。本研究的目的是评估雌二醇化学递送系统（E2-CDS）与等摩尔剂量的戊酸雌二醇-17（E2-VAL）对去势大鼠交配行为的影响。数据显示，单剂量的E2-CDS在刺激爬跨行为（反应百分比）方面比E2-VAL更有效，并且这种效果在5周内一直保持在100%。在28天内，E2-CDS比E2-VAL更能增加插入行为。与E2-VAL相比，E2-CDS在更大程度上且在更长时间（28天）内缩短了爬跨和插入潜伏期。两种形式的雌二醇均未恢复射精参数或阴茎反射。这些数据表明，E2-CDS对雄性性行为的接受和完成成分具有强大且长效的刺激作用，推测是通过大脑局部释放雌二醇来发挥作用。
