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D-精氨酸的毒理学和药理学作用。

Toxicological and pharmacological effects of D-arginine.

作者信息

Navarro Eduardo, Alonso Simeona J, Martín Felipe A, Castellano Miguel A

机构信息

Department of Pharmacology, Faculty of Medicine, University of La Laguna, Tenerife, Spain.

出版信息

Basic Clin Pharmacol Toxicol. 2005 Sep;97(3):149-54. doi: 10.1111/j.1742-7843.2005.pto_973110.x.

Abstract

D-Arginine is extensively used in studies on L-arginine/nitric oxide pathway as an inactive form of L-arginine, even in man. In addition, it has previously been reported that this D-amino acid appears to have pharmacological activity. The present work aimed at evaluating the toxicity and pharmacology of D-arginine administered by the intraperitoneally route in albino male mice. Toxicity of D-arginine, alone as well as in the presence of propranolol and betamethasone was evaluated. D-Arginine in mice showed a light toxicity order (DL50: 2800 mg/kg). Previous injection of the beta-adrenoceptor blocker, propranolol (2 mg/kg, intraperitoneally), or betamethasone (0.5 mg/kg, intraperitoneally) produced a decrease in the toxicity of D-arginine (LD50: 3600 mg/kg, 3300 mg/kg, respectively). Also, a neuropharmacological screening of D-arginine using behavioural, neurological, autonomic, barbiturate-induced sleep time and pentylenetetrazole-induced convulsions tests were performed. D-Arginine 700 mg/kg displayed central stimulant properties, whereas a depressant profile was observed at a dose of 1400 mg/kg. In addition, D-arginine 1400 mg/kg produced a potentiation of pentobarbital sleeping time and a marked anticonvulsivant action against pentylenetetrazole.

摘要

D-精氨酸作为L-精氨酸的无活性形式,甚至在人体研究中,也被广泛用于L-精氨酸/一氧化氮途径的研究。此外,此前有报道称这种D-氨基酸似乎具有药理活性。本研究旨在评估腹腔注射D-精氨酸对白化雄性小鼠的毒性和药理学作用。评估了单独使用D-精氨酸以及在普萘洛尔和倍他米松存在的情况下D-精氨酸的毒性。小鼠体内的D-精氨酸显示出轻度毒性顺序(半数致死剂量:2800毫克/千克)。预先注射β-肾上腺素能受体阻滞剂普萘洛尔(2毫克/千克,腹腔注射)或倍他米松(0.5毫克/千克,腹腔注射)会使D-精氨酸的毒性降低(半数致死剂量分别为3600毫克/千克和3300毫克/千克)。此外,还使用行为、神经、自主神经、巴比妥酸盐诱导的睡眠时间和戊四氮诱导的惊厥试验对D-精氨酸进行了神经药理学筛选。700毫克/千克的D-精氨酸表现出中枢兴奋特性,而在1400毫克/千克的剂量下观察到抑制作用。此外,1400毫克/千克的D-精氨酸可延长戊巴比妥睡眠时间,并对戊四氮产生显著的抗惊厥作用。

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