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单胺氧化酶抑制剂治疗期间的酪胺增强作用:溴法罗明和吗氯贝胺与不可逆抑制剂的比较

Tyramine potentiation during treatment with MAO inhibitors: brofaromine and moclobemide vs irreversible inhibitors.

作者信息

Bieck P R, Antonin K H

机构信息

Human Pharmacology Institute, Ciba-Geigy, Tübingen, Federal Republic of Germany.

出版信息

J Neural Transm Suppl. 1989;28:21-31.

PMID:2794993
Abstract

Healthy ambulatory subjects were treated p.o. for 2 to 4 weeks with 6 different MAO inhibitors (MAOI). MAOI drugs were given to (n) subjects. Brofaromine (Brof): 100-150 mg/d (39); moclobemide (Mocl): 450 mg/d (8); clorgyline (Clor): 5, 10, 15 mg/d (5); selegiline (Sel): 5, 20 mg/d (7); phenelzine (Phen): 30, 45, 60 mg/d (6); tranylcypromine (TCP): 20 mg/d (12). Pressor responsiveness to oral tyramine (TYR) was assessed before, during, and after treatment. In unmedicated subjects (Cont), doses of TYR to raise systolic blood pressure by at least 30 mm Hg (PD30), ranged between 200 and 800 mg. During treatment with MAOIs, the PD30 decreased. The median effective doses (ED 50) of TYR were: Cont (n = 55): 437 mg; Sel, 20 mg/d: 96 mg; Mocl 450 mg/d: 63 mg; Brof: 100-150 mg/d: 44 mg; Phen, 60 mg/d: 33 mg; Clor, 10 mg/d: 43 mg; CP: 8 mg. Pressor responsiveness to oral TYR normalized within 3 d (Mocl), 8 d (Brof), and 30 d (TCP). After Phen, in 2 subjects the potentiation persisted for 2 and 4 weeks, in 4 volunteers for 8 and more weeks. After Clor, only one of 4 subjects reached 83% of his early pressor sensitivity within 15 weeks. The results suggest that the two reversible MAO-A inhibitors Mocl and Brof may lessen the liability to TYR-related hypertensive reactions.

摘要

健康门诊受试者口服6种不同的单胺氧化酶抑制剂(MAOI)进行2至4周的治疗。将MAOI药物给予(n)名受试者。溴法罗明(Brof):100 - 150毫克/天(39人);吗氯贝胺(Mocl):450毫克/天(8人);氯吉兰(Clor):5、10、15毫克/天(5人);司来吉兰(Sel):5、20毫克/天(7人);苯乙肼(Phen):30、45、60毫克/天(6人);反苯环丙胺(TCP):20毫克/天(12人)。在治疗前、治疗期间和治疗后评估对口服酪胺(TYR)的升压反应性。在未用药的受试者(对照)中,使收缩压至少升高30毫米汞柱(PD30)的酪胺剂量在200至800毫克之间。在用MAOI治疗期间,PD30降低。酪胺的半数有效剂量(ED50)为:对照(n = 55):437毫克;司来吉兰,20毫克/天:96毫克;吗氯贝胺450毫克/天:63毫克;溴法罗明:100 - 150毫克/天:44毫克;苯乙肼,60毫克/天:33毫克;氯吉兰,10毫克/天:43毫克;反苯环丙胺:8毫克。对口服酪胺的升压反应性在3天(吗氯贝胺)、8天(溴法罗明)和30天(反苯环丙胺)内恢复正常。苯乙肼治疗后,2名受试者的增强作用持续2周和4周,4名志愿者持续8周及更长时间。氯吉兰治疗后,4名受试者中只有1人在15周内恢复到其早期升压敏感性的83%。结果表明,两种可逆性单胺氧化酶A抑制剂吗氯贝胺和溴法罗明可能会降低与酪胺相关的高血压反应的风险。

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