Neurochemical, neuroautonomic and neuropharmacological acute effects of sibutramine in healthy subjects.
Sibutramine is a neuropharmacological drug that exerts central (CNS) and peripheral effects including noradrenaline (NA), and serotonin (5-HT) uptake inhibition. In addition, the drug is able to induce release from DA axons. We measured levels of circulating neurotransmitters in 20 healthy subjects during supine-resting (fasting) state before and after 15 mg of oral sibutramine. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were also monitored. Sibutramine triggered sustained and progressive increase of NA, NA/Ad ratio and DBP. Slight increases of DA were also registered between the 60 and 240 min periods. The rise in DA tended to fade progressively, reaching basal level at 360 min period. Diastolic blood pressure, but neither SBP nor HR, showed significant increases that correlated positively with NA/Ad ratios. Slight but significant negative correlation was also found between DBP and DA. This correlation tended to fade throughout the trial to show no significance at the 360 min period. Although neither plasma serotonin (f-5HT) nor platelet serotonin (p-5HT) values showed significant variation throughout the trial, the f-5HT/p-5HT ratio showed significant decrease throughout. Significant negative correlation was found between f-5HT/p-5HT ratio and NA/Ad ratio. Our results indicate that sibutramine stimulates neural sympathetic activity but not adrenal sympathetic activity in healthy individuals. Further, sibutramine lowers parasympathetic activity. The moderate rise in diastolic blood pressure triggered by sibutramine would be associated with CNS-NA enhancement plus parasympathetic inhibition.
Lechin
Fuad
F
Department of Neurophysiology, Instituto de Medicina Experimental, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Apartado 80.983, Caracas 1080-A, Venezuela. flechin@telcel.net.ve
van der Dijs
Bertha
B
Hernandez
Gerardo
G
Orozco
Beatriz
B
Rodriguez
Simon
S
Baez
Scarlet
S
D000928:Antidepressive Agents / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects*; D001679:Biogenic Amines / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D002490:Central Nervous System / Q000187:drug effects; D002853:Chromatography, Liquid; D003503:Cyclobutanes / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D009415:Nerve Net / Q000187:drug effects; D017933:Peripheral Nervous System / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects
D000928:Antidepressive Agents; D001679:Biogenic Amines; D002395:Catecholamines; D003503:Cyclobutanes; D007202:Indicators and Reagents; C058254:sibutramine