Class III antiarrhythmic agents have been considered to lengthen the myocardial 
effective refractory period (ERP) without any significant effects on the 
conduction velocity. However, recent investigations have clarified the positive 
or negative dromotropic effects of these agents. Amiodarone, a representative 
class III agent, exerts negative dromotropism by suppressing the fast sodium 
current responsible for conduction in acute administration (class I effects). 
Chronic amiodarone causes prolongation of ERP (class III effects), which is 
sometimes associated with negative dromotropism based on the alteration of 
passive or active membrane properties. Sotalol shows neither significant 
positive nor negative dromotropism under the normoxic condition, whereas this 
agent is reported to exert positive dromotropism mediated by the cAMP-dependent 
facilitation of gap junctional electrical coupling under the hypoxic condition. 
Some pure class III agents such as nifekalant are suspected to elicit 'apparent' 
positive dromotropism in the premature impulse propagation. This is explained by 
the right and upward shift of the strength-interval curve, which theoretically 
transforms the graded premature response to the all-or-none response. Although 
the clinical relevancy of these phenomena remains to be investigated, such 
variable dromotropism of the individual class III agent may contribute to the 
better understanding and development of antiarrhythmic agents.