Pharmacological profile of enantiomerically pure chiral muscarinic agonists: Desoxymuscarines

• Published in: Life sciences (1973) 2000-06, Vol.67 (3), p.317-326
• Main Authors: De Amici, Marco, Dallanoce, Clelia, De Micheli, Carlo, Angeli, Piero, Marucci, Gabriella, Cantalamessa, Franco, Sparapassi, Lorenzo
• Format: Article
• Language: English
• Subjects: Animals; Desoxymuscarine enatinomers; Guinea Pigs; Heart Rate - drug effects; Ileum - drug effects; In Vitro Techniques; Male; Muscarine - analogs & derivatives; Muscarine - pharmacology; Muscarine enantiomers; Muscarinic Agonists - isolation & purification; Muscarinic Agonists - pharmacology; Muscarinic receptor subtypes; Muscle Contraction - drug effects; Myocardial Contraction - drug effects; Rats; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Stereoisomerism; Structure-Activity Relationship; Urinary Bladder - drug effects
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(00)00618-4

The enantiomers desoxymuscarine 6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M 2 (heart force and rate) and M 3 (ileum and bladder) receptor subtypes together with the enantiomers of the parent compound muscarine 1. The eutomers (+)-1 and (+)-6 and distomers (−)-1 and (−)-6 were also assayed in vivo on pithed rat. Affinity, relative efficacy and enantioselectivity were also determined for the compounds under study at M 2 (heart force and rate) and M 3 (ileum and bladder), in order to investigate muscarinic receptor heterogeneity. The results of this study have been discussed in comparison with the data previously reported for the structurally related fluoromuscarine (+)-4 and difluoromuscarines (+)-5 and (−)-5.