Pharmacological profile of enantiomerically pure chiral muscarinic agonists: desoxymuscarines.
The enantiomers desoxymuscarine 6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M2 (heart force and rate) and M3 (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 enantio-selectivity were also determined for the compounds under study at M2 (heart force and rate) and M3 (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.
De Amici
M
M
Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Italy.
Dallanoce
C
C
De Micheli
C
C
Angeli
P
P
Marucci
G
G
Cantalamessa
F
F
Sparapassi
L
L
D000818:Animals; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009116:Muscarine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000302:isolation & purification / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects
D018721:Muscarinic Agonists; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D009116:Muscarine