Effects of subcutaneous and intracerebroventricular administration of the sigma receptor ligand 1,3-Di-o-tolylguanidine on body temperature in the rat: interactions with BMY 14802 and rimcazole.
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.
Department of Pharmacology, School of Medicine, University of California, Los Angeles.
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M
Bejanian
R N
RN
Pechnick
M P
MP
Bova
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R
George
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology*; D004347:Drug Interactions; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D002227:Carbazoles; D006146:Guanidines; D011743:Pyrimidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; C034931:rimcazole; C050232:1,3-ditolylguanidine