Affinity profile of the novel muscarinic antagonist, guanylpirenzepine.
The study reports the functional affinity of an amidino derivative of pirenzepine, guanylpirenzepine, for muscarinic receptors mediating relaxation of rat duodenum, inhibition of rabbit vas deferens twitch contraction (both receptors previously classified as M1), guinea pig negative inotropism (M2) and ileal contraction (M3). Unlike pirenzepine, guanylpirenzepine discriminated between duodenum and vas deferens receptors, with a 30-fold greater affinity for the former subtype. The unique selectivity pattern of guanylpirenzepine (duodenum greater than vas deferens greater than ileum greater than atrium) renders it a promising tool for the classification of muscarinic receptor subtypes.
Micheletti
R
R
Dept. of Pharmacology, Istituto De Angeli, Milano, Italy.
Schiavone
A
A
Angelici
O
O
Duranti
P
P
Giudici
L
L
Cereda
E
E
Donetti
A
A
D000818:Animals; D016275:Atrial Function; D004386:Duodenum / Q000502:physiology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D008297:Male; D009116:Muscarine / Q000037:antagonists & inhibitors*; D018727:Muscarinic Antagonists; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology*; D014649:Vas Deferens / Q000502:physiology
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C066403:guanylpirenzepine; D010890:Pirenzepine; D006147:Guanine; D009116:Muscarine