Ureta H, López L F, Pérez A, Huidobro-Toro J P
Eur J Pharmacol. 1987 Mar 31;135(3):289-95. doi: 10.1016/0014-2999(87)90677-7.
(+)-Tifluadom injected i.p. produced a biphasic response of urine output: within the first hour of its administration the drug produced antidiuresis followed by a diuretic phase. In contrast, the (-) isomer produced a modest reduction in urine output as compared to the output of the saline-treated rats. In addition, (+)-tifluadom markedly reduced the output of urinary Na+ and K+. The effects of (+)-tifluadom were blocked by 7.5 mg/kg naloxone but not by 10 mg/kg of the benzodiazepine antagonist Ro 15-1788. Parallel experiments demonstrated that the i.v. administration of (+)-tifluadom to non-anesthetized rats caused a dose-related pressor response that lasted for at least 15 min. This effect of (+)-tifluadom was blocked and antagonized by naloxone. In contrast, (-)-tifluadom was either inactive on the cardiovascular system or produced short-lasting hypotension. In pentobarbital-anesthetized rats, 100 micrograms/kg (+)-tifluadom caused a precipitous hypotension that was reversed by naloxone but not by Ro 15-1788.
腹腔注射(+)-替氟朵产生尿量的双相反应：给药后的第一小时内药物产生抗利尿作用，随后是利尿期。相比之下，与生理盐水处理的大鼠相比，(-)异构体使尿量略有减少。此外，(+)-替氟朵显著降低尿钠和钾的排出量。(+)-替氟朵的作用被7.5mg/kg纳洛酮阻断，但未被10mg/kg苯二氮䓬拮抗剂Ro 15 - 1788阻断。平行实验表明，对未麻醉大鼠静脉注射(+)-替氟朵会引起剂量相关的升压反应，持续至少15分钟。(+)-替氟朵的这种作用被纳洛酮阻断并拮抗。相比之下，(-)-替氟朵对心血管系统无活性或产生短暂的低血压。在戊巴比妥麻醉的大鼠中，100μg/kg(+)-替氟朵引起急剧的低血压，可被纳洛酮逆转，但不能被Ro 15 - 1788逆转。
