M.E. Lechin

The serotonin uptake-enhancing drug tianeptine suppresses asthmatic symptoms in children: a double-blind, crossover, placebo-controlled study.

Studies have shown that levels of free serotonin in plasma are increased in symptomatic patients with asthma. In addition, the concentration of free serotonin in symptomatic patients with asthma correlates positively with clinical status and negatively with pulmonary function. Thus, reducing the concentration of free serotonin in plasma might be useful in treating patients with asthma. We studied the effectiveness of tianeptine in treating patients with asthma. Tianeptine is the only drug known to be able to reduce levels of free serotonin in plasma and to enhance uptake by platelets. In this study, 69 children with asthma were assigned in randomized fashion to receive tianeptine and/or placebo in a double‐blind crossover trial that lasted 52 weeks. Tianeptine provoked a dramatic and sudden decrease in both clinical rating and free serotonin plasma levels and an increase in pulmonary function.

Neuropharmacologic treatment of bronchial asthma with the antidepressant tianeptine: A double‐blind, crossover placebo‐controlled study

Studies have shown the levels of free serotonin in plasma are increased in symptomatic patients with asthma. In addition, the concentration of free serotonin in symptomatic children with asthma correlates positively with clinical status and negatively with pulmonary function (forced expiratory volume in 1 second [FEV1]). Thus, reducing the concentration of free serotonin in plasma may be useful in treating children with asthma. We studied the effectiveness of tianeptine in treating these patients. Tianeptine is the only drug known to be able to reduce the level of free serotonin in plasma and to enhance the uptake by platelets. Sixty‐nine of the 82 children with asthma initially enrolled participated in this study. Children were randomized to receive tianeptine or placebo or both in a double‐blind crossover trial. The trial lasted 52 weeks. Tianeptine provoked a dramatic and sudden decrease of both clinical rating and free serotonin plasma levels and an increase in pulmonary function.

Effects of buspirone on plasma neurotransmitters in healthy subjects

Summary. Buspirone is an anxiolytic drug which exerts several central effects. It antagonizes presynaptic inhibitory DA2 autoreceptors at dopaminergic neurons and acts as an agonist for 5-HT1A inhibitor autoreceptors at serotonergic cells. Thus, buspirone respectively enhances and depresses the firing rates of both type of neurons. At doses which correlate with dopaminergic stimulation, but not 5-HT inhibition, buspirone also increases the firing rates of the central noradrenergic cells. We measured levels of circulating neurotransmitters before and up to 240 minutes after the oral administration of 20 mg of buspirone in 32 healthy volunteers. Buspirone significantly increased levels of noradrenaline, dopamine, and free serotonin but did not affect levels of adrenaline, tryptophane, or platelet serotonin. Small but significant drops in systolic blood pressure and heart rate were observed after buspirone ingestion. Atropine administration before buspirone ingestion annulled the free serotonin increase as well as systolic blood pressure-heart rate decrease. We found significant positive correlations between noradrenaline and dopamine levels. The strength and significance of these correlations were increased by using the noradrenaline/adrenaline ratio instead of noradrenaline absolute values. This finding indicates that increases in both noradrenaline and dopamine arise from sympathetic nerves rather than the adrenal glands. We also found significant negative correlations between free serotonin increases and systolic blood pressure-heart rate decreases. Our results indicate that buspirone stimulates central sympathetic activity. These acute effects of buspirone are reflected in an increased peripheral neural sympathetic activity, but not adrenal sympathetic activity in healthy individuals. In addition, buspirone increases free serotonin plasma concentrations and decreases systolic blood pressure plus heart rate levels through mechanisms associated with parasympathetic activation.

Effects of amantadine on circulating neurotransmitters in healthy subjects.

Considering that glutamatergic axons innervate the C1(Ad) medullary nuclei, which are responsible for the excitation of the peripheral adrenal glands, we decided to investigate catecholamines (noradrenaline, adrenaline and dopamine) plus indolamines (plasma serotonin and platelet serotonin) at the blood level, before and after a small oral dose of amantadine, a selective NMDA antagonist. We found that the drug provoked a selective enhancement of noradrenaline plus a minimization of adrenaline, dopamine, plasma serotonin and platelet serotonin circulating levels. Significant enhancement of diastolic blood pressure plus reduction of systolic blood pressure and heart rate paralleled the circulating parameter changes. The above findings allow us to postulate that the drug was able to enhance the peripheral neural sympathetic activity. Minimization of both adrenal sympathetic and parasympathetic activities was also registered after the amantadine challenge. The above findings supported the postulation that this drug should be a powerful therapeutic tool for treating diseases affected by adrenal sympathetic hyperactivity.

Plasma Catecholamines and Chronic Congestive Heart Failure

To the Editor: We read with great interest the paper by Swedberg et al.1 With respect to it, we will supply additional information that might aid in the understanding of the failure of imidazoline’s agonists to improve chronic congestive heart failure (CCHF) in patients. We have assessed all plasma neurotransmitters in some 30 000 normal and diseased subjects. Included were noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet serotonin, free serotonin in the plasma, and tryptophan. These parameters were measured during supine-resting, 1-minute orthostasis, 5 minutes of moderate exercise,2 and after the administration of clonidine.3 We found that the normal NA/Ad ratio >4.5. This ratio is greatly reduced in stressed mammals and severely diseased humans (<1).2 With respect to the above, neural sympathetic activity (sympathetic nerves) is …