Journal article
The effects of nitric oxide synthase inhibitors on the sedative effect of clonidine
Anesthesia and analgesia, Vol.93(5), pp.1217-1221
2001
DOI: 10.1097/00000539-200111000-00035
PMID: 11682401
Abstract
The mechanism underlying the Niteroi, Rio de Janeiro sedative effect of clonidine, an alpha2-adrenoceptor agonist, remains uncertain. Because activation of alpha2-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 N(G)-nitro-L-arginine-methyl-ester (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 alpha2-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.
Details
- Title: Subtitle
- The effects of nitric oxide synthase inhibitors on the sedative effect of clonidine
- Creators
- Roberto SOARES DE MOURA - Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, BrazilAnna Amélia S RIOS - Department of Pharmacology, Fluminense Federal University, Niteroi, Rio de Janeiro, BrazilLuiz F DE OLIVEIRA - Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, BrazilAngela C RESENDE - Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, BrazilMiguel NETO DE LEMOS - Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, BrazilEdmar J. A SANTOS - Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, BrazilMarcelo L. G CORREIA - Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, BrazilTania TANO - Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
- Resource Type
- Journal article
- Publication Details
- Anesthesia and analgesia, Vol.93(5), pp.1217-1221
- Publisher
- Lippincott
- DOI
- 10.1097/00000539-200111000-00035
- PMID
- 11682401
- ISSN
- 0003-2999
- eISSN
- 1526-7598
- Language
- English
- Date published
- 2001
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094481802771
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