Gillett M K, Snashall P D
Department of Medicine, Charing Cross and Westminster Medical School, London, UK.
Eur Respir J. 1988 Jan;1(1):27-33.
The bronchial response of six normal and six asthmatic subjects to increasing concentrations of methacholine aerosol was measured by serial measurements of specific airways conductance (sGaw) in a body plethysmograph. On separate days, the subjects were premedicated with 0.9% NaCl, inhaled atropine at four different doses, or intravenous atropine at two different doses. Cumulative log dose-response curves were constructed. The provocative dose of methacholine needed to cause a 35% fall in sGaw was measured from each curve (PD35). The antagonism produced by a given atropine dose was quantified as the dose ratio, which was defined as the ratio of PD35 after atropine to PD35 after saline. In normal subjects, approximately equal amounts of atropine given by the inhaled or intravenous routes produced mean dose ratios of almost identical value. However, in asthmatic subjects inhaled atropine (1.28 mg, 4.4 mumol) produced a mean dose ratio 7.5 times greater than the mean value seen with intravenous atropine (1.0 mg, 3.46 mumol). Intravenous atropine (1.0 mg, 3.46 mumol) produced a mean dose ratio of 18.3 for all subjects, compared to a value of 26 predicted from in vitro experiments. The slope of the regression line for the relationship of log (dose ratio -1) vs -log atropine dose (Schild plot) for all subjects was -0.99. The actions we have observed are compatible with the main actions of atropine being that of a competitive antagonist at the muscarinic receptor. The greater blocking effect of inhaled atropine in some asthmatics suggests that a higher concentration of atropine is achieved at the muscarinic receptor by the inhaled route in these subjects.
通过在体容积描记器中连续测量比气道传导率（sGaw），测定了6名正常受试者和6名哮喘受试者对递增浓度的乙酰甲胆碱气雾剂的支气管反应。在不同的日子里，受试者分别预先给予0.9%氯化钠、四种不同剂量的吸入阿托品或两种不同剂量的静脉注射阿托品。构建累积对数剂量-反应曲线。从每条曲线中测量使sGaw下降35%所需的乙酰甲胆碱激发剂量（PD35）。将给定阿托品剂量产生的拮抗作用量化为剂量比，剂量比定义为阿托品给药后PD35与生理盐水给药后PD35的比值。在正常受试者中，经吸入或静脉途径给予的阿托品量大致相等，产生的平均剂量比几乎相同。然而，在哮喘受试者中，吸入阿托品（1.28 mg，4.4 μmol）产生的平均剂量比是静脉注射阿托品（1.0 mg，3.46 μmol）所见平均值的7.5倍。静脉注射阿托品（1.0 mg，3.46 μmol）对所有受试者产生的平均剂量比为18.3，而体外实验预测的值为26。所有受试者的log（剂量比 -1）与-log阿托品剂量关系的回归线斜率（希尔曲线）为-0.99。我们观察到的这些作用与阿托品作为毒蕈碱受体竞争性拮抗剂的主要作用相符。吸入阿托品在一些哮喘患者中具有更大的阻断作用，这表明在这些受试者中，通过吸入途径在毒蕈碱受体处可达到更高浓度的阿托品。
