(-)PPAP: A new and selective ligand for sigma binding sites

Abstract

Most agents employed for the investigation of sigma (α) binding sites display relatively low affinity for these sites, bind both at α sites and at either phencyclidine (PCP) sites or dopamine receptors with similar affinity, and/or produce some dopaminergic activity in vivo. We describe a new agent, (-)PPAP or R(-)-N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane hydrochloride, that binds with high affinity and selectivity at α (IC50 = 24 nM) versus either PCP sites (IC50 > 75,000 nM) or D1 and D2 dopamine receptors (IC50 > 5,000 nM). The α affinity of this agent is comparable to that of the standard ligands (+)-3-PPP and DTG. Furthermore, although (-)PPAP is structurally related to amphetamine, it neither produces nor antagonizes amphetamine-like stimulus effect in rats trained to discriminate 1 mg/kg of S(+)amphetamine from saline. © 1990.