Binding affinities of four tricyclic antidepressive drugs to muscarinic cholinergic receptors in human parotid gland.

The binding kinetics of tritiated quinuclidinyl benzilate (QNB) were studied in membrane preparations from human parotid and rabbit submandibular glands. Inhibition of 3H-QNB was then used to compare the anticholinergic activity of lofepramine, desipramine, imipramine and amitriptyline for muscarinic receptor in the salivary glands. The apparent dissociation constant (KD) for 3H-QNB binding in human parotid and rabbit submandibular gland was 33 and 61 pM and the Bmax value 507 and 169 f mol/mg protein, respectively. The mean values for the inhibition constant (Ki) for lofepramine, desipramine, imipramine and amitriptyline in human parotid gland were 285, 135, 102 and 13 nM, respectively. Very similar values were obtained for the rabbit submandibular gland. The binding affinity of tricyclic antidepressants for muscarinic cholinergic receptor sites in human parotid gland closely paralleled clinical data on the inhibition of salivary flow by these drugs.