Effect of Trazodone on the Rat Cerebral Hemodynamics.
- Author:
Jae Yong HONG
1
;
Won Tan BYOUN
;
Hwa Kyoung SHIN
;
Su Yeon KO
;
Won Suk LEE
Author Information
1. Department of Psychiatry, Yangsan Hospital, Yangsna, Kyungnam, Korea.
- Publication Type:Original Article
- Keywords:
Trazodone;
Cerebral hemodynamics;
m-Chlorophenylpiperazine;
5-HT(2A/2C) receptors
- MeSH:
Animals;
Basilar Artery;
Cytochrome P-450 Enzyme System;
Hemodynamics*;
Humans;
Ketanserin;
Laser-Doppler Flowmetry;
Male;
Microscopy, Video;
Rats*;
Rats, Sprague-Dawley;
Ritanserin;
Trazodone*;
Vasoconstriction
- From:Korean Journal of Psychopharmacology
1999;10(1):71-79
- CountryRepublic of Korea
- Language:Korean
-
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.
