Effects of propranolol, pindolol and atenolol after multiple administration in rats on the duration of hexobarbital sleeping time and on the activity of some drug-metabolizing enzyme systems.

A Kastelova, T Stoytchev
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Abstract

Three beta-adrenergic blocking agents propranolol (50 mg/kg), pindolol (5mg/kg) and atenolol (150mg/kg) were administered orally in rats for 21 days. The duration of hexobarbital (HB) sleeping time and the activities of some liver monooxygenases and synthetases were studied. The HB sleeping time was not changed. Propranolol and pindolol decreased the ethylmorfin-N-demethylase (EMND) and benzphetamine-N-demethylase (BND) activities. The three beta-adrenergic blocking agents did not change the activities of anilinehydroxylase (AH), ethoxycoumarine-O-demethylase (ECOD), and glutathione-S-transferase (G-S-T), the total content of cytochrome P-450, b5 and microsomal heme. They increased the activities of uridinediphosphoglucuronil transferase (UDPGT) and NADPH-cytochrome C reductase. The participation of different mechanisms of the effects of the three beta-adrenergic blocking agents on the activity of drug-metabolizing enzyme systems was discussed.

普萘洛尔、品多洛尔和阿替洛尔多次给药对大鼠六巴比妥睡眠时间及部分药物代谢酶系统活性的影响。
大鼠口服3种β -肾上腺素能阻滞剂心得安(50 mg/kg)、品多洛尔(5mg/kg)和阿替洛尔(150mg/kg) 21 d。研究了六巴比妥(HB)睡眠时间的持续时间和肝脏中一些单加氧酶和合成酶的活性。HB睡眠时间不变。心得安和品多洛尔降低了乙基莫芬- n-去甲基化酶(EMND)和苯丙胺- n-去甲基化酶(BND)活性。3种β -肾上腺素能阻滞剂对大鼠苯胺羟化酶(AH)、乙氧基香豆素- o -去甲基化酶(ECOD)和谷胱甘肽- s -转移酶(G-S-T)活性、细胞色素P-450、b5和微粒体血红素总含量均无影响。增加了尿苷二磷酸葡萄糖醛酸转移酶(UDPGT)和nadph -细胞色素C还原酶的活性。讨论了三种β -肾上腺素能阻滞剂对药物代谢酶系统活性影响的不同机制。
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