Fuller R W, Kurz K D, Mason N R, Cohen M L
Eur J Pharmacol. 1986 Jun 5;125(1):71-7. doi: 10.1016/0014-2999(86)90084-1.
Xylamidine and BW501C67 (alpha-anilino-N-2-m-chlorophenoxypropylacetamidine), serotonin antagonists that have been reported not to cross the blood-brain barrier, were compared to other serotonin antagonists: mianserin, ketanserin, metergoline and LY 53857. All six compounds were potent inhibitors of the binding of tritiated spiperone to 5HT2 receptors in rat frontal cortex membranes in vitro and were less potent inhibitors of the binding of tritiated serotonin to 5HT1 receptors in rat brain membranes. All were potent antagonists of the 5HT2 receptor-mediated contractile response to serotonin in the rat jugular vein in vitro. At doses of 0.1 and 0.3 mg/kg i.p., xylamidine and BW501C67 antagonized the pressor response to intravenously injected serotonin in pithed rats. In contrast, neither xylamidine nor BW501C67 at doses of 1 or 3 mg/kg i.p. antagonized the elevation of serum corticosterone concentration by quipazine in rats, although the other compounds antagonized this effect with ED50 values between 0.03 and 0.9 mg/kg. These data corroborate the previously reported antiserotonin activity of xylamidine and BW501C67. Since xylamidine and BW501C67 were potent antagonists of a peripheral serotonergic response in vivo, their inability to antagonize the elevation of serum corticosterone concentration by quipazine suggests that this effect results from activation of central serotonin receptors.
木拉米定和BW501C67（α-苯胺基-N-2-间氯苯氧基丙基乙脒）是据报道不能穿过血脑屏障的5-羟色胺拮抗剂，将它们与其他5-羟色胺拮抗剂进行了比较：米安色林、酮色林、麦角乙脲和LY 53857。所有六种化合物在体外都是大鼠额叶皮质膜中氚化螺哌隆与5HT2受体结合的强效抑制剂，而对大鼠脑膜中氚化5-羟色胺与5HT1受体结合的抑制作用较弱。所有这些化合物在体外都是大鼠颈静脉中5HT2受体介导的对5-羟色胺收缩反应的强效拮抗剂。腹腔注射剂量为0.1和0.3mg/kg时，木拉米定和BW501C67可拮抗脊髓麻醉大鼠对静脉注射5-羟色胺的升压反应。相比之下，腹腔注射剂量为1或3mg/kg时，木拉米定和BW501C67均不能拮抗喹哌嗪引起的大鼠血清皮质酮浓度升高，尽管其他化合物能拮抗此效应，其半数有效剂量（ED50）值在0.03至0.9mg/kg之间。这些数据证实了先前报道的木拉米定和BW501C67的抗5-羟色胺活性。由于木拉米定和BW501C67在体内是外周5-羟色胺能反应的强效拮抗剂，它们不能拮抗喹哌嗪引起的血清皮质酮浓度升高，这表明该效应是由中枢5-羟色胺受体激活所致。
