Effects of desmethylimipramine on plasma norepinephrine, pulse, and blood pressure

We followed the effects of a tricyclic antidepressant selective for norepinephrine (NE) uptake inhibition, desmethylimipramine (DMI), on blood pressure, heart rate, and plasma NE level in healthy subjects. After a single oral dose of 100 mg DMI, supine systolic and diastolic blood pressure and supine and upright heart rate rose, and there was an increment in heart rate with standing. After long-term low doses of the drug (mean daily dosage 67.5 mg), the upright level and increment with standing in plasma NE also rose. Supine NE levels also rose after the long-term higher dose (mean daily dosage 125 mg). No differences in any measures were detected between the short- and the two long-term dose levels of DMI. Our findings suggest that NE uptake inhibition induces physiologic elevation of NE concentration in the sympathetic neuroeffector region. A similar effect at synapses in the CNS might be involved in the mechanism of antidepressant action.