New analogues of oxotremorine and oxotremorine-M: estimation of their in vitro affinity and efficacy at muscarinic receptor subtypes.
Two subsets of tertiary amines (1a-6a) and methiodides (1b-6b) with a structural resemblance to oxotremorine and oxotremorine-M were tested at rabbit vas deferens (M1), guinea pig left atrium (M2), guinea pig ileum and urinary bladder (M3) muscarinic receptor subtypes. The pharmacological profile of the derivatives under study has been discussed by evaluating their potency, affinity and efficacy as well as the regional differences in muscarinic receptor occupancy.
Barocelli
E
E
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Parma, viale delle Scienze-Campus Università, 43100 Parma, Italy.
Ballabeni
V
V
Bertoni
S
S
Dallanoce
C
C
De Amici
M
M
De Micheli
C
C
Impicciatore
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011817:Rabbits; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D006571:Heterocyclic Compounds; D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D010095:Oxotremorine