The Cpg And Its Analogues Anticholinergic Effects

Muscarinic acetylcholine receptors (M receptors) are widely found in the peripheral tissues and the central nervous system. M receptors are very important in the functions of many apparatus and tissues. To search for effective and selective antagonists of the muscarinic receptors, we synthesized Phencynonate Hydrochloride (CPG) and its derivatives. In this article we investigate their anticholinergic potency by using radioligand binding assay with muscarinic acetylcholine receptors from rat cerebral cortex and animal functional experiments ( potentiating the effect of subthreshold hypnotic dose of sodium pentobarbital; inhibiting oxotremorine induced salivation; inhibiting the contractile response to carbachol and nicotinamide ). The results are: Anticholinergic potency of the derivatives of CPG.To explore the anticholinergic activities of CPG derivatives, affinity and relative efficacy of these reagents were tested by using radioligand binding assay with muscarinic acetylcholine receptors from rat cerebral cortex. The results showed that : The order of potency of these compounds to inhibit the binding of [3H] quinuclidinyl benzilate ( [3H] QNB ) is: 031221 is the most potent one, and its IC50 is 4.19×10-10± 3.19×10-10 M; 031022 and 031124 are 1.24×10-9± 9.46×10-10 M, 2.22×10-9± 9.88×10-10 M respectively; The IC50 of P010416,031122,031120 is in the 10-8M level; The IC50 of (S)-SHRZ, 8018-C2H5Br, SHRZ-CH3Br, 031121, 031104 is in the 10 -7M level; The IC50 of (R)-SHRZ, 8018-CH3Br, 031110 is in the 10-6M level. The compare of potent to inhibit Ach-induced contractile response SHRZ-CH3Br is the most potent one to inhibit ach-induced contractileresponse .8018-C2H5Br, 031022, 8018-CH3Br, 031120 is less potent than SHRZ-CH3Br and more potent than 031124. 031121 is the least potent one. Compare the potent of antisalivation and antagonizing nicotinamide-induced convulsion of 031221, 031022, 031124...