Effects of Midodrine on Chlorpromazine-Induced Orthostatic Hypotension in Rabbits : Comparison with Amezinium, Etilefrine and Droxidopa

元データ 2000-12-01 公益社団法人日本薬学会

概要

Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45° head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine<etilefrine<amezinium<droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine=droxidopa≧etilefrine>amezinium. Midodrine (3 mg/kg, i.d.)mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at α_1-adrenoceptors and subsequently recovers reflex vasconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics.

著者

KURIHARA Junichi Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University
OKUBO Yoko Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University
TAKATA Yoshinobu Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University
KATO Hitoshi Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University
Suzuki Shigeo Department Of Microbiology Tohoku Pharmaceutical University
Kato H Department Of Pharmacology Faculty Of Pharmaceutical Sciences Teikyo University
Takata Yoshinobu Department Of Gastroenterology National Kyushu Cancer Center
Takata Y Department Of Pharmacology Faculty Of Pharmaceutical Sciences Teikyo University
Okubo Y Department Of Pharmacology Faculty Of Pharmaceutical Sciences Teikyo University
Okubo Yoko Department Of Ecological Engineering Toyohashi University Of Technology
Suzuki Shigeto Department Of Civil Engineering Technical College Yamaguchi University
Kato Hitoshi Department Of Pediatrics Kurume University School Of Medicine
Kurihara Junichi Department Of Pharmacology Faculty Of Pharmaceutical Sciences Teikyo University
Suzuki Shigeo Department Of Applied Biological Chemistry The University Of Tokyo
Kato Hitoshi Department Of Pediatrics Graduate School Of Medicine University Of Tokyo
TAKATA Yoshinobu Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo
KATO Hitoshi Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo

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