Affinity of nortriptyline and its E-10-hydroxy metabolite for muscarinic receptors.
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.
Nilvebrant
L
L
Kabi Pharma, Urology/Gynaecology, R & D, Stockholm, Sweden.
Nordin
C
C
D000818:Animals; D001667:Binding, Competitive; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009661:Nortriptyline / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism
D011976:Receptors, Muscarinic; C013567:10-hydroxynortriptyline; D009661:Nortriptyline