Synthesis and evaluation of optically pure [3H]‐(+)‐pentazocine, a highly potent and selective radioligand for σ receptors

FEBS Letters

Rice, Kenner C.²  de Costa, Brian R.²  Walker, J.Michael¹  Hellewell, Susan B.³  Bowen, Wayne D.³  Jacobson, Arthur E.²  Thurkauf, Andrew² 

[1] Department of Psychology, Brown University, Providence, RI 02912, USA;Laboratory of Medicinal Chemistry, National Institute of Digestive, Diabetes, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA;Section of Biochemistry, Division of Biology and Medicine, Brown University, Bethesda, MD 20892, USA

关键词: Pentazocine;    (+)-[3H]-;    Receptor;    σ;    Scatchard analysis;    Radiolabeling;   

DOI  :  10.1016/0014-5793(89)81427-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tritium-labeled (+)-pentazocine ([³H]-1b) of specific activity 26.6 Ci/mmol was synthesized in 3 steps starting with (+)-normetazocine (2) of defined optical purity. [³H]-1b has been characterized as a highly selective ligand for labeling of σ receptors. Competition data revealed that [³H]-1b could be displaced from guinea pig brain membrane preparations with a number of commonly used σ receptor ligands. [³H]-1b exhibited saturable, enantioselective binding with a K _d of 5.13±0.97 nM and a B _max of 1146±122 fmol/mg protein. Phencyclidine (PCP) displaced [³H]-1b with low affinity while MK-801 was inactive, thus indicating insignificant activity at the PCP-binding site; apomorphine failed to displace [³H]-1b indicating lack of dopamine receptor cross-reactivity. Since the affinity of [³H]-1b is about 6 times that of the two commonly employed σ ligands ((+)-3-[³H]PPP and [³H]DTG) and since it is more selective for σ receptors than the benzomorphan [³H]SKF-10,047, it represents the first example of a highly selective benzomorphan based σ receptor ligand. [³H]-1b should prove useful for further study of the structure and function of σ receptors.

【 授权许可】

Unknown