In vivo labeling of sigma receptors in mouse brain with [3H]4-phenyl-1-(4-phenylbutyl)piperidine.
4-Phenyl-1-(4-phenylbutyl)piperidine (4-PPBP) is a very potent ligand for sigma (Sigma) receptors. The present study was undertaken to evaluate [3H]4-PPBP as a radioligand for in vivo labeling of cerebral sigma receptors. After intravenous administration of [3H]4-PPBP to mice, there is high uptake of radioactivity in the brain. The regional distribution of radioactivity in the brain 2 h after intravenous injection of [3H]4-PPBP parallels the in vitro binding of the radioligand in rat brain (pons/medulla > cerebellum > or = prefrontal cortex > or = parietal cortex > hypothalamus > olfactory tubercle > or = thalamus > hippocampus > striatum). Pretreatment with haloperidol (2 mg/kg) significantly decreases the radioactivity measured in the brain 30-120 min after injection of [3H]4-PPBP. Pretreatment with unlabeled 4-PPBP or ifenprodil also significantly decreases radioactivity in the brain 2 h after injection of [3H]4-PPBP, in a dose-dependent manner. The in vivo binding of [3H]4-PPBP in the brain also is significantly inhibited by SL 82.0715, BMY 14802, 1,3-di-o-tolylguanidine (DTG), and (+)-enantiomers of pentazocine, SKF 10,047, and 3-PPP, but not by the corresponding (-)-enantiomers, consistent with stereoselectivity of inhibition obtained in in vitro binding studies. In contrast, pretreatment with dizocilpine and spiperone does not inhibit in vivo binding of [3H]4-PPBP. The results indicate that [3H]4-PPBP would be a suitable radioligand for in vivo labeling of sigma receptors in brain.
Hashimoto
K
K
Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.
Scheffel
U
U
London
E D
ED
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism*
D008024:Ligands; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; C094850:4-phenyl-1-(4-phenylbutyl)piperidine; D006220:Haloperidol; C010739:ifenprodil