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KMID : 0361519990100010080
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Korean Journal of Psychopharmacology
1999 Volume.10 No. 1 p.80 ~ p.89
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Effect of Antipsychotic Drugs on the Rat Cerebral Hemodynamics
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Jung Bong-Ju
Byun Won-Tan
Lee Won-Suk
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Abstract
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Objectives：This study was designed to investigate the effect of antipsychotic drugs (chlorpromazine, haloperidol and clozapine) on the cerebral hemodynamics including the changes in regional cerebral blood flow (rCBF) and the pial arteriolar diameter of male Sprague-Dawley rats.
Methods：The changes in rCBF were determined by laser-Doppler flowmetry, and the changes in diameter of pial arteriole were measured through a closed cranial window.
Results：Clozapine (0.1~10 μg/kg, i.v. or 0.03~3 μM) caused an increase in rCBF in association with a vasodilation of pial arteriole in a dose-dependent manner, whereas chlorpromazine and haloperidol (5~500 μg/kg, i.v., respectively) were without effect on rCBF. Clozapine-induced increases in rCBF were significantly blocked by topical pretreatment with NMDA receptor blockers (MgCl2, MK-801, ketamine and D(-)-2-amino-5-phosphonopentanoic acid). Constitutive nitric oxide synthase inhibitors (NG-nitro-L-arginine, 7-nitroindazole and diphenyleneiodonium) markedly inhibited the clozapine-induced increases in rCBF. However, aminoguanidine, an inducible nitric oxide synthase inhibitor did not affect the clozapine-induced increases in rCBF. Inhibitors of soluble guanylyl cyclase (methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) significantly attenuated the clozapine-induced increases in rCBF.
Conclusion：These results suggest that typical antipsychotic drugs are without effect on rCBF, but atypical antipsychotic drug clozapine exerts an increase in rCBF with pial arteriolar dilation via mediation of NMDA receptor stimulation, and thereby, leading to activation of neuronal and endothelial nitric oxide synthases and increase in cyclic GMP formation.
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KEYWORD
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Antipsychotic drugs, Cerebral hemodynamics, NMDA receptor,
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