Affinity of nortriptyline and its E-10-hydroxy metabolite for muscarinic receptors

Abstract

In the present investigation, the binding of nortriptyline and its active metabolite 10-hydroxynortriptyline (E-10-OH-NT) to muscarinic receptors was studied in the heart, parotid gland, cerebral cortex, urinary bladder and ileum from guinea pig. The affinity of E-10-OH-NT, as determined by competition with 1-quinuclidinyl (phenyl 4-3H)benzilate (-)3H-QNB), was about 10-12 times lower than that of nortriptyline in each tissue and none of the compounds seemed to exhibit any tissue selectivity. It is concluded that increased heart rate induced by E-10-OH-NT, but not by nortriptyline, cannot be attributed to a selective blockade of cardiac muscarinic receptors.