SYNTHESIS AND EVALUATION OF OPTICALLY PURE [H-3] (+)-PENTAZOCINE, A HIGHLY POTENT AND SELECTIVE RADIOLIGAND FOR SIGMA-RECEPTORS
SYNTHESIS AND EVALUATION OF OPTICALLY PURE [H-3] (+)-PENTAZOCINE, A HIGHLY POTENT AND SELECTIVE RADIOLIGAND FOR SIGMA-RECEPTORS
复制标题
DOI：
10.1016/0014-5793(89)81427-9
复制
发表时间：
1989-07-17
期刊：
影响因子：
3.5
通讯作者：
RICE, KC
中科院分区：
文献类型：
--
作者：
DECOSTA, BR;BOWEN, WD;RICE, KC
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 aKdof 5.13±0.97 nM and aBmaxof 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.
