Wu X Z, Bell J A, Spivak C E, London E D, Su T P
Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, Maryland 21224.
J Pharmacol Exp Ther. 1991 Apr;257(1):351-9.
Whole cell voltage clamp studies were performed on NCB-20 cells to examine physiological responses to drugs possessing affinities for sigma receptors. Those drugs [haloperidol, alpha-(4-fluoro-phenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutano l (BMY-14802), pentazocine, N-allylnormetazocine (SKF-10047), 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP), phencyclidine, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine maleate (MK-801)] caused an apparent inward current, which was due to blockade of a tonic, outward potassium current. The rank order of drug potencies in producing this effect generally resembled the rank orders of sigma-receptor affinities for the drugs, except that a reverse stereoselectivity was observed for several drugs. 3H-SKF-10047 labeled two sites in intact NCB-20 cells (Kd = 49 nM, Bmax = 1.0 pmol/mg protein and Kd = 9.6 microM, Bmax = 69 pmol/mg protein). The high affinity site was similar pharmacologically to the sigma receptor assayed in membrane fragments from NCB-20 cells. However, the low affinity site showed a slightly different profile, highlighted by a reverse stereoselectivity. The rank order of drug potencies was as follows at the low affinity site: haloperidol greater than BMY-14802 greater than (-)-pentazocine greater than (+)-pentazocine greater than (-)-SKF-10047 greater than (-)-3-PPP greater than (+)-SKF-10047 greater than (+)-3-PPP greater than phencyclidine greater than TCP greater than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)
