Reyes-Parada M, Scorza C, Romero V, Silveira R, Medina J H, Andrus D, Nichols D E, Cassels B K
Cell Biology Division, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Naunyn Schmiedebergs Arch Pharmacol. 1996 Nov;354(5):579-85. doi: 10.1007/BF00170831.
Serotonergic behavioral responses, effects on motor activity and core temperature, and binding properties of the novel putative anxiolytic amphetamine derivative (+/-)1-(2,5-dimethoxy-4-ethylthio-phenyl)-2-aminopropane (ALEPH-2), were examined in rodents in order to elucidate the mechanism underlying its anxiolytic-like effect. After peripheral administration in rats, ALEPH-2 induced some symptoms of the serotonergic syndrome, e.g. forepaw treading and flat body posture. Additionally, a decrease in motor activity was observed. No significant effects on the number of head shakes were observed after injection, although high inter-subject variability was noted. Higher doses of ALEPH-2, in the range exhibiting anxiolytic properties (4mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT2A/2C receptors ([3H]ketanserin sites) was in the nanomolar range (Ki = 173 nM), whereas for 5-HT1A, benzodiazepine sites, and GABAA receptors, the affinity was micromolar of lower. Based on these results the mechanism of action and the anxiolytic-like properties of ALEPH-2 are discussed.
为阐明新型假定抗焦虑苯丙胺衍生物（±）1-（2,5-二甲氧基-4-乙硫基苯基）-2-氨基丙烷（ALEPH-2）的抗焦虑样作用机制，在啮齿动物中研究了其5-羟色胺能行为反应、对运动活性和核心体温的影响以及结合特性。在大鼠外周给药后，ALEPH-2诱发了一些5-羟色胺能综合征的症状，如前爪踩踏和平躺姿势。此外，观察到运动活性降低。注射后未观察到对摇头次数有显著影响，尽管个体间差异较大。在表现出抗焦虑特性的剂量范围（4mg/kg）内，较高剂量的ALEPH-2可使小鼠体温显著降低。该药物对5-HT2A/2C受体（[3H]酮色林位点）的亲和力处于纳摩尔范围（Ki = 173 nM），而对5-HT1A、苯二氮䓬位点和GABAA受体的亲和力为微摩尔或更低。基于这些结果，讨论了ALEPH-2的作用机制和抗焦虑样特性。
