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

Abstract

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.

Desipramine inhibits salivary Ca2+ signaling and aquaporin translocation

“…Finally, the results of the adrenergic antagonist experiment confirm that the effect of desipramine is not mediated by catecholamine reuptake inhibition or adrenergic potentiation, which are unique characteristics of tricyclic antidepressants. In fact, tricyclic antidepressants including desipramine are reported to show a binding affinity to muscarinic and histamine receptors (Taylor and Richelson, ; Batra and Biörklund, ; Somogyi and Perel, ). Due to the similar characteristics of these receptors, some antihistamine drugs (i.e., diphenhydramine and promethazine) block muscarinic receptors (Liu et al , ; Brown and Eckberg, ), which possibly explains the inhibitory specificity of desipramine.…”

Altered Responses to Agonists after Chronic In Vivo Atropine Administration in Rat Parotid Acini

“…Effect of Chronic Atropine Treatment on Agonist-Induced Ca2+ Mobilization and IP Turnover. Several classes of drugs produce salivary gland hypofunction by interfering with stimulus-secretion coupling of the muscarinic receptor (Batra and Biorklund, 1986;Clemmensen, 1988;Dissing et al, 1990;Unden et al, 1989; Van der Ven et al, 1986).…”

“…Many commonly prescribed medications such as antidepressant and antipsychotic drugs have potent antimuscarinic properties (Batra and Biorklund, 1986;Clemmensen, 1988;Dissing et al, 1990;Unden et al, 1989; Van der Ven et al, 1986). The oral complications of reduced salivary flow are well documented (see Melvin, 1991), for example, an increased susceptibility to dental decay, bacterial and fungal infections, and mucositis.…”