Spitzmaul_1999_Neuroreport_10_2175

Non-competitive inhibitors (NCIs) of the nicotinic receptors (AChR) comprise a wide range of compounds. The chemical scaffold of amphetamine is similar to those of some NCIs. We investigated the effects of amphetamine (1-100 microM) on the muscle AChR by recording single-channel currents. The drug reduces the duration of the open state in a concentration-dependent manner and causes the appearance of brief closings, resembling the action of open-channel blockers. The forward rate constant for the blocking process is of the order of 10(7) M(-1) s(-1) and the blocking process is voltage dependent. The results are consistent with the steric block of the open channel as the primary action of amphetamine. At high drug concentrations the mechanism of inhibition deviates from that of classical open-channel blockers.