Wolff M C, Leander J D
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Pharmacol Biochem Behav. 1994 Oct;49(2):385-91. doi: 10.1016/0091-3057(94)90438-3.
Ditolyguanidine (DTG) induced a dose-dependent emetic response in pigeons, with 100% of the birds vomiting after 5.6 mg/kg. Retching and vomiting originally induced by DTG could be conditioned to the test situation. Both the unconditioned and conditioned emetic responses were dose-dependently blocked by 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT) and LY228729, agonists at the 5-HT1A subtype of serotonin receptor, but not by the 5-HT3, antagonist tropisetron. Higher doses (0.25-0.5 mg/kg) of tropisetron exhibited intrinsic emetic activity which could also be prevented by 8-OH-DPAT. NAN-190, a putative 5-HT1A partial agonist, produced both an antiemetic response when administered before DTG and also attenuated the antiemetic effects of 8-OH-DPAT. Pentobarbital blocked the conditioned, but not the unconditioned DTG-induced emesis. These results support the possibility that 5-HT1A agonists exhibit antiemetic activity against a broad range of emetic stimuli, including conditioned vomiting which is usually resistant to pharmacological attenuation.
二托利胍（DTG）在鸽子中引起剂量依赖性催吐反应，5.6毫克/千克后100%的鸟类呕吐。DTG最初引起的干呕和呕吐可与测试情境形成条件反射。5-羟色胺受体5-HT1A亚型的激动剂8-羟基-（二正丙基氨基）四氢萘（8-OH-DPAT）和LY228729剂量依赖性地阻断了非条件性和条件性催吐反应，但5-HT3拮抗剂托烷司琼没有。更高剂量（0.25-0.5毫克/千克）的托烷司琼表现出内在催吐活性，8-OH-DPAT也可预防这种活性。NAN-190是一种假定的5-HT1A部分激动剂，在DTG给药前给药时产生抗呕吐反应，并且还减弱了8-OH-DPAT的抗呕吐作用。戊巴比妥阻断了条件性，但未阻断非条件性DTG诱导的呕吐。这些结果支持了5-HT1A激动剂对广泛的催吐刺激表现出抗呕吐活性的可能性，包括通常对药物减弱有抗性的条件性呕吐。
