Hudzik T J, De Costa B R, McMillan D E
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock.
Eur J Pharmacol. 1993 May 19;236(2):279-87. doi: 10.1016/0014-2999(93)90599-d.
In order to more fully characterize sigma ligand-induced emesis in the pigeon, the effects of a number of compounds were tested alone or in combination with ditolyguanidine (DTG). The drugs tested could be categorized into three types: agonists, which produced the emetic response (DTG > amitriptyline > BD 737 > thioridazine), antagonists, which effectively antagonized the effects of DTG (haloperidol > BMY 14802 > BD 1139 > chlorpromazine), and agents which did not produce the emetic response on their own, but potently enhanced the emetic effect of DTG (BD-1008 > or = phencyclidine > (+)-n-allylnormetazocine > or = propranolol). Chronic haloperidol resulted in a markedly diminished emetic response to DTG, which returned to control levels by 24.5 days. Haloperidol, but not BMY 14802, was effective in antagonizing the lethal effects of DTG. These data suggest further in vivo evidence for a functional mediation by sigma sites of the emetic response to DTG in the pigeon, and may provide in vivo evidence for potential allosteric modification of sigma ligands.
为了更全面地描述鸽子中σ配体诱导的呕吐，测试了多种化合物单独或与二对甲苯基胍（DTG）联合使用的效果。所测试的药物可分为三类：产生呕吐反应的激动剂（DTG＞阿米替林＞BD 737＞硫利达嗪）、有效拮抗DTG作用的拮抗剂（氟哌啶醇＞BMY 14802＞BD 1139＞氯丙嗪）以及自身不产生呕吐反应但能显著增强DTG呕吐作用的药物（BD - 1008≥苯环利定＞（+）-N -烯丙基去甲唑新≥普萘洛尔）。长期给予氟哌啶醇会导致对DTG的呕吐反应明显减弱，到24.5天时恢复到对照水平。氟哌啶醇而非BMY 14802能有效拮抗DTG的致死作用。这些数据进一步提供了体内证据，表明鸽子中DTG呕吐反应通过σ位点进行功能介导，并且可能为σ配体的潜在变构修饰提供体内证据。
