Mohamed A S, Forray C, Aly M H, el-Fakahany E E
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore 21201.
Eur J Pharmacol. 1992 Oct 1;227(2):181-7. doi: 10.1016/0922-4106(92)90126-g.
We assessed the intrinsic activity of the purported selective muscarinic M1 receptor agonist SR 95639A (morpholinoethylamino-3-benzocyclohepta-(5,6-c)-pyridazine) in inducing several receptor-mediated signals. Our results indicate that SR 95639A lacks the ability to activate phosphoinositide hydrolysis in rat cerebral cortex or in Chinese hamster ovary cells transfected with the genes of the muscarinic m1 and m3 receptors. Similarly, this compound did not exhibit intrinsic activity in stimulating muscarinic receptors which inhibit cyclic AMP synthesis and did not suppress acetylcholine release in rat striatum. In addition, SR 95639A did not show a marked selectivity at the level of the ligand recognition site at the muscarinic M1, M2 and M3 receptors, since it bound to these receptor subtypes with equilibrium dissociation constants of 4, 6 and 11 microM, respectively.
我们评估了所谓的选择性毒蕈碱M1受体激动剂SR 95639A（吗啉代乙基氨基-3-苯并环庚并-(5,6-c)-哒嗪）诱导多种受体介导信号的内在活性。我们的结果表明，SR 95639A缺乏激活大鼠大脑皮层或转染了毒蕈碱m1和m3受体基因的中国仓鼠卵巢细胞中磷酸肌醇水解的能力。同样，该化合物在刺激抑制环磷酸腺苷合成的毒蕈碱受体方面未表现出内在活性，并且在大鼠纹状体中也未抑制乙酰胆碱释放。此外，SR 95639A在毒蕈碱M1、M2和M3受体的配体识别位点水平上未表现出明显的选择性，因为它分别以4、6和11微摩尔的平衡解离常数与这些受体亚型结合。
