Berlin I, Warot D, Aymard G, Acquaviva E, Legrand M, Labarthe B, Peyron I, Diquet B, Lechat P
Department of Pharmacologie, Groupe Hospitalier Universitaire, Pitié-Salpêtrière, Paris, France.
Eur J Clin Pharmacol. 2001 Sep;57(6-7):447-55. doi: 10.1007/s002280100317.
To determine the cardiovascular, subjective effects and potential of abuse liability of single dose (-) ephedrine (E) administered orally (50 mg) or intranasally (10 mg and 5 mg).
Sixteen healthy Caucasian men with no history of drug/alcohol/nicotine abuse or dependence received intranasal single doses of E 5 mg, 10 mg and oral doses of 50 mg and placebo in a double-blind, double-dummy, crossover study. Dependent measures included assessment of subjective feelings by Addiction Research Centre Inventory (ARCI). Profile of Mood States (POMS). visual analogue scales (VAS); "drug liking", "any drug effect", subjective quality of sleep and blood pressure and heart rate. Plasma E concentrations were also determined.
(-) E increased supine systolic, diastolic blood pressure (P < 0.01). Changes in supine systolic blood pressure (areas under the 8 h of the experimental sessions) were -59 +/- 47 mmHgh with placebo, -59 +/- 57 mmHg-h with E5 mg by the nasal route, -18 +/- 48 mmHg x h with E 10 mg by the nasal route and 13 +/- 58 mmHgh with E 50 mg by the oral route (P<0.001). (-) E-induced orthostatic hypotension (P < 0.01) (maximal systolic blood pressure drop: E 50 mg 14 +/- 10 mmHg, P < 0.03; E 10 mg 11 +/- 6 mmHg, P = 0.08 compared with placebo) and resulted in decreased tiredness (placebo -2 +/- 39 mm x h, E 5 mg -17 +/- 39 mm x h, E 10 mg -30 +/- 42 mm x h, E 50 mg -24 +/- 35 mm x h; P < 0.03). E did not modify ARCI subscales--in particular the "amphetamine" subscale--but showed a tendency for drug liking (P= 0.09). On the "any drug effect" questionnaire, subjects could identify drug effect (P=0.007). Maximal plasma E concentration (Cmax) and areas under the curves for up to 8 h were proportional to the doses. Elimination half-life was approximately 6 h. A clockwise hysteresis was observed for systolic blood pressure in all but one subject with E 50 mg by the oral route.
E even at low doses and by the nasal route can decrease tiredness in healthy persons; this is accompanied by a substantial increase in blood pressure and orthostatic hypotension exposing individuals in case of intensive physical exercise to cardiovascular risks. No clear evidence of abuse liability in healthy drug naive subjects was observed.
确定口服（50毫克）或鼻内给药（10毫克和5毫克）单剂量（-）麻黄碱（E）的心血管作用、主观效应及滥用倾向可能性。
16名无药物/酒精/尼古丁滥用或依赖史的健康白人男性，在一项双盲、双模拟、交叉研究中接受鼻内单剂量5毫克、10毫克的E以及口服50毫克的E和安慰剂。相关测量包括通过成瘾研究中心量表（ARCI）评估主观感受、情绪状态剖面图（POMS）、视觉模拟量表（VAS）；“药物喜好度”、“任何药物效应”、睡眠主观质量以及血压和心率。还测定了血浆E浓度。
（-）E使仰卧位收缩压和舒张压升高（P<0.01）。仰卧位收缩压变化（实验时段8小时内的曲线下面积），安慰剂组为-59±47毫米汞柱·小时，鼻内给药5毫克E组为-59±57毫米汞柱·小时，鼻内给药10毫克E组为-18±48毫米汞柱·小时，口服给药50毫克E组为13±58毫米汞柱·小时（P<0.001）。（-）E引起体位性低血压（P<0.01）（最大收缩压下降：口服50毫克E为14±10毫米汞柱，P<0.03；鼻内给药10毫克E为11±6毫米汞柱，与安慰剂相比P = 0.08），并导致疲劳感减轻（安慰剂组为-2±39毫米·小时，5毫克E组为-17±39毫米·小时，10毫克E组为-30±42毫米·小时，50毫克E组为-24±35毫米·小时；P<0.03）。E未改变ARCI分量表，尤其是“苯丙胺”分量表，但显示出药物喜好倾向（P = 0.09）。在“任何药物效应”问卷中，受试者能够识别药物效应（P = 0.007）。最大血浆E浓度（Cmax）和8小时内的曲线下面积与剂量成正比。消除半衰期约为6小时。除一名口服50毫克E的受试者外，所有受试者均观察到收缩压呈顺时针滞后现象。
即使是低剂量且通过鼻内给药的E也能减轻健康人的疲劳感；这伴随着血压大幅升高和体位性低血压，在剧烈体育锻炼时会使个体面临心血管风险。在无药物使用史的健康受试者中未观察到明显的滥用倾向证据。
