Up-regulation of rat cortical sigma receptors after subchronic administration of rimcazole and 1,3-di(2-tolyl)guanidine.
The effects of subchronic administration of rimcazole and 1,3-di(2-tolyl)guanidine (DTG) on the central R(+)[3H]-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine (R(+)[3H]-3-PPP) binding site were investigated in the rat. Subchronic treatment with rimcazole was characterized by a 30% increase in the density and a two-fold decrease in the affinity of R(+)[3H]-3-PPP binding sites relative to saline-treated animals. DTG, a more potent sigma ligand, produced a similar alteration to the affinity but a 130% increase in the density of R(+)[3H]-3-PPP binding sites. These data thus provide evidence for the functional involvement of sigma receptors in the central nervous system.
Manallack
D T
DT
University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Austin Hospital, Heidelberg, Victoria, Australia.
Beart
P M
PM
D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma
D002227:Carbazoles; D006146:Guanidines; D010880:Piperidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; C026539:preclamol; C034931:rimcazole; C050232:1,3-ditolylguanidine