Lucot J B, Brame R E L, Garrett T L, Pfadenhauer E H, Kumar A, Fick D B, Helton D R
Department of Pharmacology, Wright State University, Dayton, OH, USA,
Exp Brain Res. 2014 Aug;232(8):2699-707. doi: 10.1007/s00221-014-4004-z. Epub 2014 Jun 10.
In the present study, we describe how a nonstoichiometric ratio of the isomers of 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT) produce a broad-spectrum of antiemetic effects in cats and shrews. Determination of the receptor profile of the isomers and testing them separately in cats revealed superior antiemetic effects but severe defensive behavior with the R isomer compared with the S isomer. Differing ratios yielded the best results with the 1:8 (R-S) ratio producing a drug more potent than DPAT and with negligible defensive behavior side effects. Studies with selective 5-HT1D ligands led to the conclusion that this site contributes antiemetic efficacy but is not related to defensive behavior, which is most likely a consequence of 5-HT7 receptor activation. ETI-385 was effective in preventing emetic responses to provocative motion, drugs acting at the chemical trigger zone and cisplatin in both cats and shrews. The results support a clinical trial of this drug for antiemetic effects.
在本研究中，我们描述了8-羟基-2-（二正丙基氨基）四氢萘（DPAT）异构体的非化学计量比如何在猫和鼩鼱中产生广泛的止吐作用。对异构体的受体谱进行测定并在猫中分别测试后发现，与S异构体相比，R异构体具有更强的止吐作用，但会引发严重的防御行为。不同比例产生了最佳结果，1:8（R-S）比例产生的药物比DPAT更有效，且防御行为副作用可忽略不计。使用选择性5-HT1D配体的研究得出结论，该位点有助于止吐效果，但与防御行为无关，防御行为很可能是5-HT7受体激活的结果。ETI-385在预防猫和鼩鼱对刺激性运动、作用于化学触发区的药物和顺铂的催吐反应方面有效。这些结果支持对该药物进行止吐作用的临床试验。
