Cardiocirculatory effects of Ro 11-2464, a selective 5-HT (serotonin) uptake inhibitor, in healthy volunteers

Summary

The imipramine derivative Ro 11-2465, a potent, selective 5-HT (serotonin) uptake inhibitor, is being developed as an antidepressant agent. The effects of Ro 11-2465 on heart rate, blood pressure, electrocardiogram and systolic time intervals were assessed in nine normotensive volunteers. Ro 11-2465 1 and 2 mg and a placebo were given in a single blind, cross over design study. The placebo did not induce any significant changes. With Ro 11-2465, the ECG-intervals (P,PQ,QRS,QTc) did not change, the blood pressure increased 3–6 h after administration of either dose, and the heart rate was increased 4–6 h after the 2 mg dose. There was also evidence of increased ventricular automaticity in one subject. The total electromechanical systole (QS₂-index) was significantly shortened 4–8 h after administration of 2 mg, whereas neither 1 mg the dose nor the placebo had any such effect. This finding suggests the presence of a positive inotropic effect, which is probably due to a stimulatory effect of serotonin, and is not mediated by an adrenergic mechanism. The findings suggest that Ro 11-2465, as a potential new tricyclic antidepressant, might have favourable cardiocirculatory side effects, particularly in patients with pre-existing heart disease.