Effect of Trazodone on the Rat Cerebral Hemodynamics / 대한정신약물학회지
Korean Journal of Psychopharmacology
; : 71-79, 1999.
Artigo
em Coreano
| WPRIM (Pacífico Ocidental)
| ID: wpr-201658
Biblioteca responsável:
WPRO
ABSTRACT
OBJECTIVES:
The present study assessed the effect of trazodone on the cerebral hemodynamics of male Sprague-Dawley rats.METHOD:
The changes of regional cerebral blood flow(rCBF) and pill arterial diameter were measured by laser-Doppler flowmetry and by a videomicroscopy, respectively. The changes in vascular tone and intracellular free Ca2+ concentration ([Ca2+]i) of isolated basilar artery were simultaneously measured using a small vessel myograph and a cation measurement system, respectively.RESULT:
Both the rCBF and the pill arterial diameter were dose-dependently decreased by systemic administration of trazodone(0.3-10 mg/kg, i.v.), but not by topical application of trazodone(10-300 micrometer). Pretreatment with 5-HT(2A/2C) receptor antagonist(ketanserin or ritanserin, 1 mg/kg, i.v., respectively) significantly blocked the changes in rCBF induced by trazodone. m-Chlorophenylpiperazine(mCPP ; 0.1-3 mg/kg, i.v. or 5-500 micrometer topical), a major active metabolite of trazodone, also dose-dependently decreased the rCBF as well as the pial arterial diameter. The mCPP-induced decreases in rCBF were significantly blocked by ketanserin. Pretreatment with itraconazole(1 mg/kg, p.o.), a selective inhibitor of CYP3A4, a subfamily of cytochrome P450, markedly attenuated the trazodone-induced changes in rCBF. In an isolated rat basilar arterial strip loaded with fura-2/AM, mCPP(5-500 micrometer caused a vasoconstriction in association with increases in [Ca2+]i, in a concentration-dependent manner. Pretreatment with 1 micrometerketanserin strongly blocked the effects of mCPP on the vascular tone as well as on the [Ca2+]i, of rat basilar artery.CONCLUSION:
These results suggest that trazodone decreases rCBF through stimulation of 5-HT(2A/2C) receptors by its active metabolite, mCPP.
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Trazodona
/
Vasoconstrição
/
Artéria Basilar
/
Ketanserina
/
Ritanserina
/
Ratos Sprague-Dawley
/
Fluxometria por Laser-Doppler
/
Microscopia de Vídeo
/
Sistema Enzimático do Citocromo P-450
/
Hemodinâmica
Limite:
Animais
/
Humanos
/
Masculino
Idioma:
Coreano
Revista:
Korean Journal of Psychopharmacology
Ano de publicação:
1999
Tipo de documento:
Artigo