VARIATION IN THE AFFINITY OF AMITRIPTYLINE FOR MUSCARINE RECEPTOR SUBTYPES

The affinity of amitriptyline for muscarine M(1) receptors was studied in the rat cerebral cortex and rabbit vas deferens utilizing binding studies as well as inhibition of carbachol-induced phosphoinositide hy drolysis in the cerebral cortex and blockade of the muscarinic prejunc tional inhibition of sympathetic nerve stimulation in the rabbit vas d eferens. The inhibition constants (K-I) or dissociation constants (K-B ) Obtained were approximately 6- to 20-fold lower than those obtained at muscarine M(2) receptors in rat atria (binding and negative inotrop ic response) indicating that amitriptyline exhibits a degree of muscar ine M(1) receptor selectivity.