Pouzet Bruno
H. Luncbeck A/S, Department of Psychopharmacology, Ottiliavej 7-9, Dk-2500 Valby, Denmark.
CNS Drug Rev. 2002 Spring;8(1):90-100. doi: 10.1111/j.1527-3458.2002.tb00217.x.
Recently, a series of 5-HT7 receptor antagonists have been developed (24,29,36,68). Among them SB-258741, R-(+)-1-(toluene-3-sulfonyl)-2-[2-(4-methylpiperidin-1-yl)ethyl]-pyrrolidine, (compound "13" in 36,37) was one of the most potent and specific compounds. Due to a lack of specific ligands the pharmacology of 5-HT7 receptor antagonists is still relatively unexplored. It has been suggested, however, that 5-HT7 receptor ligands could be useful in the therapy of various disorders such as sleep disorders, schizophrenia, depression, migraine, epilepsy, pain, or memory impairment. Many of these conceivable indications are not supported by pharmacological data. It is, therefore, of particular interest to review the data generated from studies of one of these most potent and specific 5-HT7 receptor antagonists, SB-258741, with a goal of testing the validity of the proposed clinical indications. In this review, the author describes pharmacology of this compound in order to define its potential clinical use. The available safety pharmacology data are discussed in an attempt to predict potential side effects of specific 5-HT7 receptor antagonists.
最近，已开发出一系列5-羟色胺7（5-HT7）受体拮抗剂（24,29,36,68）。其中，SB-258741，即R-(+)-1-(甲苯-3-磺酰基)-2-[2-(4-甲基哌啶-1-基)乙基]-吡咯烷（36,37中的化合物“13”）是最有效且最具特异性的化合物之一。由于缺乏特异性配体，5-HT7受体拮抗剂的药理学仍相对未被充分探索。然而，有人提出5-HT7受体配体可能对治疗各种疾病有用，如睡眠障碍、精神分裂症、抑郁症、偏头痛、癫痫、疼痛或记忆障碍。这些可能的适应症中有许多并未得到药理学数据的支持。因此，特别有必要回顾一下对这些最有效且最具特异性的5-HT7受体拮抗剂之一SB-258741的研究所产生的数据，目的是检验所提出的临床适应症的有效性。在这篇综述中，作者描述了该化合物的药理学，以确定其潜在的临床用途。还讨论了现有的安全药理学数据，试图预测特异性5-HT7受体拮抗剂的潜在副作用。
