Stereoselectivity at muscarinic receptor subtypes: observations with the enantiomers of phenglutarimide.
作者： G�nter Lambrecht , Roland Feifel , Ernst Mutschler
关键词:
摘要: The affinity of the enantiomers phenglutarimide at three muscarinic receptor subtypes was examined in vitro using field-stimulated rabbit vas deferens (M1 receptors) and guinea pig atria (M2 alpha ileum beta receptors). Extremely high stereoselectivity observed higher affinities (up to 6000-fold) were found for (+)-S-enantiomer. ratios different subtypes, stereochemical demands made by receptors most stringent M1 receptors. (+)-(S)-Phenglutarimide be a potent M1-selective antagonist (pA2 = 8.53). Its selectivity profile is qualitatively similar that pirenzepine. (-)-(R)-Phenglutarimide showed no comparable discriminatory properties.
sci-hub.se 参考文章(22)
R. M. EGLEN, R. L. WHITING, MUSCARINIC RECEPTOR SUBTYPES: A CRITIQUE OF THE CURRENT CLASSIFICATION AND A PROPOSAL FOR A WORKING NOMENCLATURE Journal of Autonomic Pharmacology. ,vol. 6, pp. 323- 346 ,(1986) , 10.1111/J.1474-8673.1986.TB00661.X
Joachim Knabe, Sebastian Wahl, 2,6‐Piperidindione, 4. Mitt.: Synthese der Racemate und der Enantiomere 3,3‐disubstituierter 2,6‐Piperidindione mit basischer Seitenkette Archiv Der Pharmazie. ,vol. 320, pp. 1032- 1042 ,(1987) , 10.1002/ARDP.198700006
Magali Waelbroeck, Jean Camus, Michèle Tastenoy, Jean Christophe, 80% of muscarinic receptors expressed by the NB-OK 1 human neuroblastoma cell line show high affinity for pirenzepine and are comparable to rat hippocampus M1 receptors. FEBS Letters. ,vol. 226, pp. 287- 290 ,(1988) , 10.1016/0014-5793(88)81441-8
C. C. PFEIFFER, Optical isomerism and pharmacological action, a generalization. Science. ,vol. 124, pp. 29- 31 ,(1956) , 10.1126/SCIENCE.124.3210.29
E. K. G. Syvälahti, R. Kunelios, L. Laurén, Effects of Antiparkinsonian Drugs on Muscarinic Receptor Binding in Rat Brain, Heart and Lung Pharmacology & Toxicology. ,vol. 62, pp. 90- 94 ,(1988) , 10.1111/J.1600-0773.1988.TB01852.X
Manfrid Eltze, Volker Figala, Affinity and selectivity of biperiden enantiomers for muscarinic receptor subtypes. European Journal of Pharmacology. ,vol. 158, pp. 11- 19 ,(1988) , 10.1016/0014-2999(88)90247-6
W. L. Nelson, D. S. Freeman, F. F. Vincenzi, Stereochemical analogs of a muscarinic, ganglionic stimulant. 2. The cis and trans olefinic, epoxide, and cyclopropane analogs related to 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butynyltrimethylammonium chloride Journal of Medicinal Chemistry. ,vol. 19, pp. 153- 158 ,(1976) , 10.1021/JM00223A026
Joachim Knabe, Sebastian Wahl, 2,6-Piperidindione, 5. Mitt.: Die absoluten Konfigurationen von optisch aktiven 2,6-Piperidindionen mit basischer Seitenkette und von einem Zwischenprodukt Archiv der Pharmazie. ,vol. 320, pp. 1150- 1154 ,(1987) , 10.1002/ARDP.198700024
Ronald J. Tallarida, Alan Cowan, Martin W. Adler, pA2 and receptor differentiation: A statistical analysis of competitive antagonism Life Sciences. ,vol. 25, pp. 637- 654 ,(1979) , 10.1016/0024-3205(79)90505-8
Carlo Melchiorre, Piero Angeli, Günter Lambrecht, Ernst Mutschler, Maria T. Picchio, Jürgen Wess, Antimuscarinic action of methoctramine, a new cardioselective M-2 muscarinic receptor antagonist, alone and in combination with atropine and gallamine. European Journal of Pharmacology. ,vol. 144, pp. 117- 124 ,(1987) , 10.1016/0014-2999(87)90509-7