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福乐布特罗:一种与β-肾上腺素能激动剂相关的潜在抗抑郁药物。小鼠实验概况

Flerobuterol: a potential antidepressant drug related to beta-adrenergic agonists. Experimental profile in mice.

作者信息

Duteil J, Rambert F A, Pointeau A M, Mangiameli P, Assous E

机构信息

Centre de recherches du laboratoire L Lafon, Maisons-Alfort, France.

出版信息

Fundam Clin Pharmacol. 1991;5(8):695-708. doi: 10.1111/j.1472-8206.1991.tb00758.x.

Abstract

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.

摘要

使用经典的小鼠精神药理学测试,评估了与β-肾上腺素能受体激动剂相关的新药非诺特罗(dl-(氟-2-苯基)-1-叔丁基氨基-2-乙醇)的潜在抗抑郁作用,并与丙咪嗪和沙丁胺醇进行了比较。与丙咪嗪和沙丁胺醇一样,非诺特罗(0.5-32毫克/千克,腹腔注射)能完全预防阿扑吗啡(16毫克/千克,皮下注射)引起的体温过低,并部分逆转利血平和氧化震颤素引起的体温过低。在较高剂量(16-32毫克/千克)时,非诺特罗增强了育亨宾的毒性作用。与丙咪嗪不同,非诺特罗和沙丁胺醇在行为绝望测试中并未减少不动时间。沙丁胺醇和非诺特罗降低了运动活性。非诺特罗不会引起瞳孔散大,不能预防氧化震颤素引起的震颤或唾液腺和泪腺分泌,也不会减轻利血平引起的眼睑下垂。普萘洛尔(8毫克/千克,腹腔注射)而非α-甲基-对酪氨酸(75毫克/千克,腹腔注射)可预防非诺特罗对阿扑吗啡诱导的体温过低的拮抗作用。我们的结果表明,非诺特罗具有潜在的抗抑郁活性,这可能与小鼠体内的β-肾上腺素能受体激活有关。

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