nAChR

Mecamylamine blocks muscle nAChRs in a use- and voltagedependent manner. Mecamylamine blocks the nicotinic currents via trapping mechanism. The main feature of this block is the phenomenon of block relief, which might be revealed by combined action of depolarization and activation of nAChRs. The experimental study of the Mecamylamine action on muscle nAChRs revealed that: (1) Mecamylamine (1-20 μM) reduces evoked end-plate currents (EPC) amplitude with Hill’s constant equal to 1.2 and IC ₅₀ = 7.8 μM at holding potential –70 mV; (2) the calculated depth of its interaction with the muscle nAChR channel is almost half of the one of neuronal nAChRs (0.37 compare to 0.72 for neuronal nAChRs); (3) simultaneous membrane depolarization and repetitive activation of postsynaptic nAChRs by motor nerve stimulation produced rapid block relief dependent on the degree of depolarization, number of conditioning signals and Mecamylamine concentration, and only slightly depended on the rate of stimulation.

Mecamylamine (0.5-1 mg/kg; Intraperitoneal injection; C57BL/6J mice) has antidepressant-like effects in both the TST and FST and these effects are dependent on bothβ2 andα7 subunits.