Hudkins R L, Mailman R B, DeHaven-Hudkins D L
Albany Molecular Research, NY 12203.
Eur J Pharmacol. 1994 Dec 12;271(1):235-6. doi: 10.1016/0014-2999(94)90286-0.
RLH-033 [2-(4-phenylpiperidinyl)ethyl 1-(4-nitrophenyl)cyclopentanecarboxylate HCl] is a rationally designed ligand that was synthesized and evaluated for its binding affinities at sigma 1 and sigma 2 sites in guinea pig brain. RLH-033 has high affinity (Ki = 50 pM) for sigma 1 sites labeled by 3H-pentazocine, while it was over 2000-fold less affinity at sigma 2 sites labeled by [3H]1,3-di(2-tolyl)guanidine (DTG) in the presence of 500 nM (+)-pentazocine (Ki = 105 nM). Unlike its potent sigma activity, the compound has little affinity for dopamine D1 (Ki = 2.9 microM), D2 (Ki = 0.35 microM), muscarinic M1 (Ki = 0.88 microM) or M2 (Ki = 1.7 microM) receptors, and none at all for N-methyl-D-aspartate, phencyclidine and opioid receptors. Thus, RLH-033 is the most potent sigma 1 ligand reported to date, and its very high affinity suggests it may be a useful radioligand to characterize the pharmacology of sigma 1 recognition sites.
RLH - 033[2 - (4 - 苯基哌啶基)乙基1 - (4 - 硝基苯基)环戊烷羧酸盐酸盐]是一种经过合理设计的配体，已合成并对其在豚鼠脑内σ1和σ2位点的结合亲和力进行了评估。RLH - 033对由3H - 喷他佐辛标记的σ1位点具有高亲和力（Ki = 50 pM），而在存在500 nM(+) - 喷他佐辛的情况下，它对由[3H]1,3 - 二(2 - 甲苯基)胍（DTG）标记的σ2位点的亲和力低2000多倍（Ki = 105 nM）。与它强大的σ活性不同，该化合物对多巴胺D1（Ki = 2.9 μM）、D2（Ki = 0.35 μM）、毒蕈碱M1（Ki = 0.88 μM）或M2（Ki = 1.7 μM）受体几乎没有亲和力，对N - 甲基 - D - 天冬氨酸、苯环己哌啶和阿片受体则完全没有亲和力。因此，RLH - 033是迄今为止报道的最有效的σ1配体，其非常高的亲和力表明它可能是一种用于表征σ1识别位点药理学的有用放射性配体。
