产前苯二氮䓬免疫抑制：外周苯二氮䓬位点可能参与其中。

Prenatal benzodiazepine immunosuppression: possible involvement of peripheral benzodiazepine site.

作者信息

Schlumpf M, Parmar R, Ramseier H R, Lichtensteiger W

机构信息

Institute of Pharmacology, University of Zürich, Switzerland.

出版信息

Dev Pharmacol Ther. 1990;15(3-4):178-85. doi: 10.1159/000457643.

DOI:10.1159/000457643

PMID:1966020

Abstract

Treatment of pregnant Long Evans rats with a low dose of diazepam (1.25 mg/kg from gestational day 14-20) produced offspring suffering from suppression of cellular immune responses. Analogous effects were produced by clonazepam, a benzodiazepine (BDZ) with high affinity for the central-type, and Ro 5-4864, a BDZ with selective affinity for the peripheral-type BDZ receptor. Peripheral-type BDZ receptors are found to develop early in fetal life in peripheral organs including primary (thymus) and secondary (spleen) lymphoid organs, in the central nervous system and on immune cells (lymphocytes). In prenatally diazepam-exposed offspring the affinity constant is significantly changed. BDZ and PK 11195 also inhibit mitogen and alloantigen-induced T and B cell proliferation in vitro in adult murine lymphocytes. Diazepam, Ro 5-4864 and PK 11195 were found to be the most active compounds.

摘要

用低剂量地西泮（从妊娠第14天至20天给予1.25毫克/千克）处理怀孕的Long Evans大鼠，所产后代会出现细胞免疫反应受抑制的情况。具有对中枢型高亲和力的苯二氮䓬类药物氯硝西泮以及对周边型苯二氮䓬受体具有选择性亲和力的苯二氮䓬类药物Ro 5-4864也会产生类似效果。研究发现，周边型苯二氮䓬受体在胎儿生命早期就在包括初级（胸腺）和次级（脾脏）淋巴器官、中枢神经系统以及免疫细胞（淋巴细胞）在内的周边器官中发育。在产前暴露于地西泮的后代中，亲和常数会发生显著变化。苯二氮䓬类药物和PK 11195在体外也会抑制成年小鼠淋巴细胞中丝裂原和同种异体抗原诱导的T细胞和B细胞增殖。地西泮、Ro 5-4864和PK 11195被发现是活性最强的化合物。