The use of histamine induced bronchoconstriction as a method for investigating bronchodilator drugs

Abstract

BRONCHODILATOR drugs are often tested clinically by giving them to asthmatic patients and following the changes in some objective measurement reflecting the severity of airways obstruction such as timed fractions of the forced vital capacity (FVC), or, more specifically, changes in airways resistance itself. Pharmacologists test these drugs on experimental animals; one of the methods which they employ is to give the drug to guinea-pigs which are then exposed to atmospheres containing histamine in the form of an aerosol. Without the drug, the animals develop severe airway obstruction and may die. Active drugs, such as the majority of the sympathomimetic amines, prevent this occurrence completely in suitable dosage or at least mitigate its severity. The possibility of using a similar technique with normal human subjects has already been explored by Griffin and Turner (1971) who investigated the activity of beta-adrenergic drugs; phenoxybenzamine has also been investigated in this way by Kerr et al. (1970). Recently we have used a similar method for testing a new bronchodilator drug, erythro-(3-4 dihydroxyphenyl)2 piperidyl methanol hydrobromide. (This will be referred to as WG 253 because at present it lacks an approved chemical name. A note on the pharmacology of this drug appears in the Appendix.) We decided to use this method in normal subjects because they react reproducibly to histamine inhalation and are more readily available than asthmatic subjects; moreover airways obstruction in asthmatic subjects is, by definition, variable, sometimes over quite short periods of time, and this makes interpretation of 'before and after' studies difficult or uncertain.