Bejanian M, Pechnick R N, Bova M P, George R
Department of Pharmacology, School of Medicine, University of California, Los Angeles.
J Pharmacol Exp Ther. 1991 Jul 1;258(1):88-93.
The current study investigated the effects of the acute s.c. and i.c.v. administration of 1,3-di-o-tolylguanidine (DTG) on body temperature in rats. The effects of putative sigma receptor antagonists BMY 14802 and rimcazole on DTG-induced changes in body temperature also were evaluated. The acute s.c. administration of DTG (10.0 and 20.0 mg/kg) produced hypothermia but no observable behavioral effects. Similarly, the acute i.c.v. administration of DTG (12.0-100.0 micrograms/rat) produced hypothermia, but ataxia occurred after this route of administration. The s.c. administration of BMY 14802 alone (25.0 mg/kg) decreased body temperature and enhanced the DTG-induced hypothermia, whereas the administration of rimcazole (25.0 mg/kg) neither altered body temperature nor affected the hypothermia produced by DTG. Neither BMY 14802 nor rimcazole produced any behavioral effects when administered alone. The inability of the putative sigma receptor antagonists BMY 14802 and rimcazole to antagonize DTG-induced hypothermia suggests that either these compounds at the dose used have little sigma receptor antagonist activity, or that the DTG-induced hypothermia is not due to specific interactions with sigma receptors.
本研究调查了1,3-二邻甲苯基胍（DTG）急性皮下和脑室内给药对大鼠体温的影响。还评估了假定的σ受体拮抗剂BMY 14802和利咪唑对DTG诱导的体温变化的影响。急性皮下注射DTG（10.0和20.0mg/kg）可导致体温过低，但未观察到明显的行为影响。同样，急性脑室内注射DTG（12.0 - 100.0微克/只大鼠）也可导致体温过低，但经此给药途径后出现共济失调。单独皮下注射BMY 14802（25.0mg/kg）可降低体温并增强DTG诱导的体温过低，而注射利咪唑（25.0mg/kg）既不改变体温，也不影响DTG产生的体温过低。单独给药时，BMY 14802和利咪唑均未产生任何行为影响。假定的σ受体拮抗剂BMY 14802和利咪唑无法拮抗DTG诱导的体温过低，这表明要么所使用剂量的这些化合物几乎没有σ受体拮抗剂活性，要么DTG诱导的体温过低并非由于与σ受体的特异性相互作用所致。
