Arrang J M, Schwartz J C, Schunack W
Eur J Pharmacol. 1985 Oct 29;117(1):109-14. doi: 10.1016/0014-2999(85)90478-9.
The effects of the enantiomers of two chiral analogues of histamine (alpha, N alpha-dimethylhistamine and N alpha-methyl-alpha-chloromethylhistamine) were studied at H3-autoreceptors modulating histamine release in rat brain slices. These compounds act as H3-receptor agonists, displaying a low potency relative to histamine (below 4%) but a pronounced stereoselectivity (ratio of 31 for the isomers of alpha, N alpha-dimethylhistamine and 183 for their halogenated analogues) was observed. The (+)isomers (corresponding to S-configurated L-histidine) were highly preferred at H3-receptors, whereas the (-)isomers were more potent at H2-receptors, no difference being observed at H1-receptors. In addition, no such stereoselectivity was observed for the two isomers of a chiral impromidine derivative: both Sopromidine and its S enantiomer acted as antagonists of histamine at H3-autoreceptors with similar potencies (Ki = 5.6 X 10(-8) M and 4.5 X 10(-8) M), whereas Sopromidine acted as an H2-receptor agonist and the S-enantiomer as an H2-receptor antagonist. Our results indicate that H3-autoreceptors are chemically stereoselective, with structural requirements different from those of H1- and H2-receptors.
研究了组胺的两种手性类似物（α，Nα-二甲基组胺和Nα-甲基-α-氯甲基组胺）的对映体在调节大鼠脑片组胺释放的H3自受体上的作用。这些化合物作为H3受体激动剂，相对于组胺显示出低效力（低于4%），但观察到明显的立体选择性（α，Nα-二甲基组胺异构体的比例为31，其卤代类似物的比例为183）。（+）异构体（对应于S构型的L-组氨酸）在H3受体上高度优先，而（-）异构体在H2受体上更有效，在H1受体上未观察到差异。此外，对于手性异丙咪啶衍生物的两种异构体未观察到这种立体选择性：Sopromidine及其S对映体在H3自受体上均作为组胺拮抗剂，效力相似（Ki = 5.6×10^(-8) M和4.5×10^(-8) M），而Sopromidine作为H2受体激动剂，S对映体作为H2受体拮抗剂。我们的结果表明，H3自受体具有化学立体选择性，其结构要求不同于H1和H2受体。
