STUDIES ON PHARMACODYNAMIC ACTION OF N-ETHYLMALEIMIDE (NEM)

In isolated guinea pig atrial preparations, NEM in the concentration of 5×10-5 M to 10-4 M produced an increase in the amplitude and rate of contraction at earlier stages, resulting in inhibition of contraction accompanied by an increase in resting tension and irregularity in rate at later stages, while the diphasic actions of NEM were completely antagonized by cysteine. The initial action of NEM was blocked by propranolol, guanethidine and failed to appear in the reserpinized atria, but reappeared after incubation of atria with norepinephrine indicating that it is mediated by norepinephrine. NEM augmented the contractile response of ductus deferens to hypogastric nerve stimulation at the earlier stages, but suppressed it at later stages. The augmenting effect of NEM on the response to sympathetic nerve stimulation was dependent on calcium concentrations in suspending medium. Effects of NEM on synaptic transmission of sympathetic nerves were discussed.