Treatment of bronchial asthma with tianeptine.
Although circulating catecholamines and free serotonin in the plasma (f-5-HT) were found to be increased during asthma attacks, only f-5-HT levels correlated positively with bronchoconstriction and clinical severity. Tianeptine, a drug that enhances serotonin uptake by platelets and serotonergic axons at the central nervous system (CNS), provoked an abrupt disappearance of asthma attacks. This fact explains why tianeptine has proven to be a powerful therapeutic tool in controlling asthma. Its success has been demonstrated not only in two double-blind placebo, cross-over trials, but through an open study lasting more than seven years that included over 25,000 asthmatic patients. In the present article, we discuss the peripheral and central nervous system mechanisms that may explain the therapeutic success of tianeptine. These are summarized below. F-5-HT is taken up by pulmonary endocrine cells (PNEC) located at the parasympathetic terminals. A presynaptic element, these cells release serotonin and potentiate acetylcholine (ACh)-induced contraction of bronchial muscle. This effect is mediated by 5-HT(3) and 5-HT(4) postsynaptic receptors located at the bronchial muscle. According to the above, the increased f-5-HT plasma level, triggered by both platelet aggregation and nocturnal and/or diurnal hyperparasympathetic activity, potentiates ACh-induced bronchoconstriction. The fact that serotonin released by medullary serotonergic axons stimulates the medullary vagal cardiorespiratory neurons obliges us to think that serotonin-induced CNS mechanisms are also involved. Furthermore, the finding that drugs that interfere with serotonin uptake, by both platelets and 5-HT-terminals, worsen asthma symptoms and are able to provoke asthma attacks gives additional support to the above peripheral and CNS mechanisms.
Lechin
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F
Department of Physiological Sciences, Sections of Neurochemical, Neurophysiology, Neuroimmunology and Neuropharmacology, Instituto de Medicina Experimental, Universidad Central de Venezuela, Caracas, Venezuela. flechin@telcel.net.ve
van der Dijs
B
B
Lechin
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AE
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D002986:Clinical Trials as Topic; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D013841:Thiazepines / Q000494:pharmacology / Q000627:therapeutic use*
D018927:Anti-Asthmatic Agents; D013841:Thiazepines; C050504:tianeptine