Cardiovascular and parasympathetic effects of dexmedetomidine in healthy subjects

• Published in: Canadian journal of physiology and pharmacology 2004-05, Vol.82 (5), p.359-362
• Main Authors: Penttilä, Jani, Helminen, Antti, Anttila, Markku, Hinkka, Susanna, Scheinin, Harry
• Format: Article
• Language: English
• Subjects: Administration, Buccal; Adult; Analysis of Variance; Biological and medical sciences; Cardiovascular System - drug effects; Catecholaminergic system; Dexmedetomidine - administration & dosage; Humans; Infusions, Intravenous; Male; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Parasympathetic Nervous System - drug effects; Parasympathetic Nervous System - physiology; Pharmacology. Drug treatments
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y04-028

We evaluated the cardiovascular effects of intravenously (i.v.) and buccally administered dexmedetomidine, a selective α 2 -adrenoceptor agonist. Six healthy male subjects were studied unmedicated and after 2 µg/kg i.v. or buccal doses of dexmedetomidine, using repeated recordings of ECG and blood pressure. Cardiac parasympathetic activity was estimated by measurements of high-frequency (HF) heart rate variability. Intravenous, but not buccal, dexmedetomidine raised systolic blood pressure by 11 ± 5 mmHg (mean ± SEM) and diastolic by 16 ± 3 mmHg (maxima at 10 min). Later on, both i.v., and buccal dexmedetomidine produced a very similar hypotensive effect: on average, 10 mmHg reductions in systolic and diastolic pressure at 3 h. Intravenous dosing was followed by a decline in heart rate (-11 ± 2 beats/min) accompanied by a trend toward enhanced HF variability (maximal effect at 10 min), which probably reflected baroreflex-mediated parasympathetic efferent neuronal activation. Buccal dexmedetomidine increased significantly the HF variability (maximum at 45 min) without influencing heart rate. We conclude that dexmedetomidine, when administered by a method that avoids concentration peaks, e.g., buccal dosing, can be used to produce a prolonged augmentation of cardiac parasympathetic efferent neuronal activity.Key words: dexmedetomidine, parasympathetic nervous system, heart rate, blood pressure.