3-Chlorodibenzazepine binding to cholinergic receptors and ion channels

The interactions of 3-chlorodihydrodibenzazepines with nicotinic receptors and ion channels from Torpedo californica electric organ and muscarinic receptors from rat brain were revealed by their inhibition of the binding of specific radiolabelled probes. Desmethylchlorimipramine (DCI) was twice as active as chlorimipramine (CI) in inhibiting [3H]phencyclidine and [3H]perhydrohistrionicotoxin binding to nicotinic ion channels; inhibition constants were 0.13 and 0.28 micro M in the presence and 1.2 and 3.4 micro M in the absence of carbamylcholine. Both of the drugs had marginal affinity for the nicotinic receptor (i.e., the [3H]3-quinuclidinyl benzilate binding to muscarinic receptors from rat brain stem and cerebral cortex with inhibitions constants below 0.1 micro M. Little regional specificity or activation by N-ethylmaleimide was apparent in the muscarinic binding of CI and DCI, properties associated with the binding of receptor antagonists.