Acute electrophysiological effects of intravenous milnacipran, a new antidepressant agent.
Milnacipran is a new antidepressant agent selected from a series of cycloproprane derivatives. The aim of this study was to investigate the acute electrophysiological effects and the tolerance of intravenous administration of this drug in 10 patients without any abnormality as shown in an electrophysiological study done for various complaints. Milnacipran was given over a 30-min period at doses of 0.2 mg/kg (2 patients), 0.4 mg/kg (2 patients) and 0.8 mg/kg (6 patients). The most significant alterations observed in this study were increases in heart rate (average of maximal increase: +19.5% at 50 min, P = 0.06) and systolic blood pressure (average of maximal increase: +21.5% at 10 min, P < 0.005), and decreases in the functional refractory period of the atrium (-3%, P < 0.05), the atrioventricular node (-9%, P < 0.005) and the effective refractory period of the right ventricle (-10.8%, P < 0.05) at 50 min. The sinus node function was improved in nine patients but depressed in one patient with previous slight baseline sinus node alterations. Milnacipran being devoid of both anticholinergic and monoamine oxidase inhibition activities, these alterations could be related to inhibition of noradrenaline uptake leading to an increase of adrenergic activities. No other ECG or electrophysiological parameters were significantly altered. Five of the 10 patients reported transient nausea, four of them for the highest dosage (0.8 mg/kg) and at the moment of peak of milnacipran plasma level. In conclusion, electrophysiological effects of intravenous milnacipran are negligible. These findings differ from those, well described in the literature, for imipramine-like antidepressant agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Caron
J
J
Service de Pharmacologie Hospitalière, Hôpital Cardiologique, C.H.R.U. de Lille, France.
Libersa
C
C
Hazard
J R
JR
Lacroix
D
D
Facq
E
E
Guedon-Moreau
L
L
Fautrez
V
V
Solles
A
A
Puozzo
C
C
Kacet
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003521:Cyclopropanes / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects
D000928:Antidepressive Agents; D003521:Cyclopropanes; D000078764:Milnacipran