A comparison between chronotropic effects of neostigmine and edrophonium in isolated guinea pig right atrium

Bradycardia is one of the inevitable and undesirable responses when the muscle weakness induced by nondepolarizing muscle relaxants is reversed by AChE inhibitors. The current study was designed to compare the bradycardiac effects of the two AChE inhibitors used widely in clinical anesthesia, neostigmine and edrophonium. Isolated, spontaneously beating guinea pig right atrial preparations were used as the experimental model, and in some cases, electrical field stimulation was utilized to stimulate parasympathetic nerve terminals within the atria. Neostigmine decreased the spontaneously beating rate in a concentration-dependent manner at concentrations up to 10 microM. At higher concentrations, the agent restored the beating rate to the predrug control level. Atropine abolished the biphasic response of the atrium to neostigmine. In contrast, edrophonium had no effect on the spontaneous beating rate. However, edrophonium (3 microM) potentiated the field stimulation-induced negative chronotropic effect. Tetrodotoxin did not inhibit the chronotropic effect of neostigmine. Both neostigmine and edrophonium at higher concentrations inhibited the negative chronotropic effect of carbachol. In conclusion, neostigmine possesses potential dual effects on cardiac muscarinic ACh receptors. Low concentrations of neostigmine may stimulate the receptors directly, and at higher concentrations neostigmine may act as an antimuscarinic agent. On the other hand, edrophonium may inhibit the cardiac muscarinic ACh receptors exclusively without stimulating the receptors. These results could at least partially explain the difference between the bradycardiac effects of the agents observed clinically.