Labeling in vivo of sigma receptors in mouse brain with [3H]-(+)-SKF 10,047: Effects of phencyclidine, (+)- and (−)-N-allylnormetazocine, and other drugs

✍ Scribed by Dr. Robert M. Ferris; Anne Russell; Flora L. M. Tang; Phillip A. Topham

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 821 KB
• Volume: 24
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.430240107

✦ Synopsis

Labeling in vivo of sigma receptors in mouse brain with [3H]-( +)-SKF 10,047: Effects of phencyclidine, ( + ) -and (-)-N-allylnormetazocine, and other drugs. Drug Dev. Res. 24:81-92, 1991. The sigma receptor, so named because of the distinct pharmacological profile produced by its prototypic agonist SKF 10,047 (N-allynormetazocine), is believed to mediate mania and psychotomimetic effects in man. While this sigma receptor has received extensive biochemical and pharmacological characterization in vitro, little information is available on the nature of the sigma site in vivo. In the present study, we examined the binding of [3H]-( +)-SKF 10,047 to sigma receptors in mouse brain in vivo and to sigma receptors in mouse and guinea pig brain in vitro and determined the relative potencies of various drugs in displacing this ligand. Mice were injected with 5 pCi of rH]-( +)-SKF 10,047 into the tail vein. After various time intervals, the mice were decapitated: their brains were rapidly removed, weighed, and homogenized in 50 mM Tris-HCI buffer, pH 7.7; and total and particulate bound radioactivity were determined. Specifically bound [3H]-( + )-SKF 10,047 in the particulate fraction was defined as the difference in total radioactivity in the particulate fraction obtained from vehicle-injected mice minus the radioactivity in the particulate fraction from haloperidol (2 mgikg i.p.)-injected mice. Specifically bound [3H]-( + )-SKF 10,047 in the particulate fraction reached peak levels of 30 min after i.v. injection and constituted 90-95% of the total particulate radioactivity. Labeling of the sigma sites could be blocked in vivo by injecting mice i.p. with the drug 30 min before the i.v. injection of the 3H-ligand. Under these