Pharmacological characterization of in vivo [3H]lfenprodil binding sites in the mouse brain.
Intravenous injection of 5 muCi of [3H]ifenprodil to mice resulted in an accumulation of radioactivity in the whole brain which was maximal at 5 min postinjection and then declined in a biphasic manner. When whole brain radioactivity was measured 2 h after [3H]ifenprodil injection, more than 65% of the incorporated label was displaced by i.p. administration (30 min before the radiotracer) of the ifenprodil chemical congener +/-alpha-(4-chlorophenyl)-4-(4- fluorophenylmethyl)-1-piperidine ethanol (SL 82.0715) (10 mg/kg). At this time, most of the radioactivity (80%) present in the brain comigrated with authentic [3H]ifenprodil. When administered 30 min before the radiotracer, several sigma ligands inhibited in vivo [3H]ifenprodil binding to the mouse brain with the following rank order of potency (ID50, mg/kg, i.p.): haloperidol (0.27) greater than ifenprodil (0.83) greater than SL 82.0715 (1.37) greater than BMY 14,802 (5.5) greater than 1,3-di-O-tolylguanidine (18). GBR 12909 (20 mg/kg, i.p.) and phencyclidine (30 mg/kg, i.p.) also inhibited this binding by 71 and 59%, respectively. In contrast, the N-methyl-D-aspartate receptor channel blockers 1-[1-(2-thienyl)cyclohexyl] piperidine and MK-801 (10 mg/kg, i.p.) failed to affect [3H]ifenprodil binding.(ABSTRACT TRUNCATED AT 250 WORDS)
Benavides
J
J
Synthélabo Recherche Biology Department, Bagneux, France.
Peny
B
B
Allen
J
J
Scatton
B
B
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D004347:Drug Interactions; D007700:Kinetics; D008297:Male; D051379:Mice; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism*; D017480:Receptors, sigma
D010880:Piperidines; D011619:Psychotropic Drugs; D011957:Receptors, Opioid; D017480:Receptors, sigma; C010739:ifenprodil