title: In vivo pharmacodynamic assays for M2 and M3 muscarinic receptors.
abstract: M(2) and M(3) muscarinic receptor subtypes are attractive drug targets for the treatment of pulmonary and urological disorders. Described in this unit is an in vivo pithed rat assay for estimating agonist and antagonist potency at M(2) and M(3) receptors. In the pithed rat, the muscarinic agonist methacholine induces reduction in heart rate (bradycardia) and blood pressure (depressor response) through interaction with M(2) and M(3) receptors, respectively. The dissociation of the peripheral and central nervous system in the pithed rat preparation permits the direct assessment of compound effects on the heart and vasculature in the absence of cardiovascular reflexes. Estimates of antagonist potency can be reliably established by quantifying the shift in the agonist dose-effect curve produced under appropriate equilibrium or non-equilibrium conditions.
authors.affiliation: Theravance, South San Francisco, California, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Armstrong
authors.forename: Tod
authors.initials: T
authors.lastname: Steinfeld
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Pulido-Rios
authors.forename: Sharath S
authors.initials: SS
authors.lastname: Hegde
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000502:physiology*
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3