(-)PPAP: a new and selective ligand for sigma binding sites.
Most agents employed for the investigation of sigma (sigma) binding sites display relatively low affinity for these sites, bind both at sigma 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 sigma (IC50 = 24 nM) versus either PCP sites (IC50 greater than 75,000 nM) or D1 and D2 dopamine receptors (IC50 greater than 5,000 nM). The sigma 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.
Glennon
R A
RA
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0540.
Battaglia
G
G
Smith
J D
JD
D000818:Animals; D002384:Catalysis; D003913:Dextroamphetamine / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects; D006168:Guinea Pigs; D006220:Haloperidol; D066298:In Vitro Techniques; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011437:Propylamines; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma
D010880:Piperidines; D011437:Propylamines; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; C068473:N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane; C026539:preclamol; D006220:Haloperidol; D003913:Dextroamphetamine