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Anesth Analg 2001;93:1217-1221
© 2001 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

The Effects of Nitric Oxide Synthase Inhibitors on the Sedative Effect of Clonidine

Roberto Soares de Moura, MD PhD*, Anna Amélia S. Rios, MD{dagger}, Luiz F. de Oliveira, MD PhD*, Ângela C. Resende, PhD*, Miguel de Lemos Neto, MD PhD*, Edmar J. A. Santos, MD*, Marcelo L. G. Correia, MD*, and Tania Tano, PhD*

*Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro; and {dagger}Department of Pharmacology, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil

Address Correspondence and reprint requests to Roberto Soares de Moura, Departamento de Farmacologia, Instituto de Biologia, Centro Biomédico, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, Rio de Janeiro, RJ, Brasil, CEP 20551-030. Address e-mail to demoura{at}uerj.br

The mechanism underlying the Niteroi, Rio de Janeiro sedative effect of clonidine, an {alpha}2-adrenoceptor agonist, remains uncertain. Because activation of {alpha}2-adrenoceptors induces release of nitric oxide (NO), we tested the hypothesis that the sedative effect of clonidine depends on NO-related mechanisms. The effect of 7-nitro indazole on the sleeping time induced by clonidine was studied in Wistar rats. In addition, we examined the effect of clonidine, {alpha}-methyldopa, and midazolam on the thiopental-induced sleeping time in rats pretreated with NG-nitro-L-arginine-methyl-esther (L-NAME). The sleeping time induced by clonidine was significantly decreased by 7-nitro indazole. Thiopental sleeping time was increased by clonidine, {alpha}-methyldopa, and midazolam. L-NAME reduced the prolongation effect of clonidine and {alpha}-methyldopa, but did not alter the effect of midazolam on the thiopental-induced sleeping time. The inhibitory effect of L-NAME on clonidine-dependent prolongation of thiopental-induced sleeping time was reversed by L-arginine. These results suggest that NO-dependent mechanisms are involved in the sedative effect of clonidine. In addition, this effect seems to be specific for the sedative action of {alpha}2-adrenoceptors agonists.

IMPLICATIONS: Clonidine, an antihypertensive drug, is also a sedative. This sedative effect, although an adverse event in the treatment of hypertensive patients, can be helpful for sedation of surgical patients. The mechanism of this effect, however, is unknown. In this study, we show that the sedative effect of clonidine is mediated by nitric oxide, because it could be prevented by pretreatment with nitric oxide synthase inhibitors.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2001 by the International Anesthesia Research Society.