Salmeterol is a new inhaled 2 adrenoceptor agonist, which has been shown in animal experiments to produce a more prolonged bronchodilator effect than currently available f2 adrenoceptor agonists. It was studied in eight adult asthmatic patients. Each patient received on separate test days salbutamol 200 pg and salmeterol 50, 100, and 200 pg according to a randomised, double blind, crossover design. FEV1, peak expiratory flow (PEF), heart rate, blood pressure, and tremor were recorded in the clinic for six hours after drug inhalation; PEF was recorded for a further six hours at home. All three doses ofsalmeterol produced peak increases in FEV1 (mean 0*5-048 1) and PEF (71-100 I/min) similar to those produced by salbutamol 200 yg (051 and 74 1/min). After salbutamol FEVy and PEF had returned to baseline within six hours, but after all three doses of salmeterol more than half of the maximum bronchodilator effect remained after 12 hours. The effects ofsalbutamol and the two lower doses ofsalmeterol (50 and 100 ug) on cardiovascular measurements and on tremor were similar, whereas after salmeterol 200 pg there was a small decrease in diastolic blood pressure and an increase in heart rate and tremor. Thus inhaled salmeterol has a long acting bronchodilator action in asthmatic patients. This effect may be of value in the treatment of asthma, particularly in patients with nocturnal symptoms.

Salmeterol (SM) is a new beta 2-adrenoceptor agonist for inhaled use that has been shown to produce long-lasting bronchodilation in asthmatic patients. In the present study, evaluating efficacy and possible development of tachyphylaxis after SM, 12 patients with stable asthma were included after the demonstration of reversibility in FEV1 of at least 15% to 200 micrograms salbutamol (SB) or 20% to 500 micrograms SB. At inclusion all patients were receiving treatment with inhaled beta 2-agonists, and 11 of the 12 patients were also receiving inhaled corticosteroids. The patients were treated for two 2-wk periods with either inhaled SM 50 micrograms twice a day or SB 200 micrograms four times a day, following a double-blind, double-dummy, randomized design. The treatment periods were separated by a washout period of 1 wk. Dose-response curves to inhaled SB were obtained the day before and the day after each treatment period. On each of these days, basal FEV1, tremor, heart rate, and blood pressure were recorded and were then followed after the inhalation of 100 + 300 + 900 micrograms SB to obtain a cumulative dose-response curve. During the treatment periods, as well as during the washout week after each treatment, the patients recorded their morning and evening peak expiratory flow (PEF) each day before the inhalation of the study drug. Subjective asthma symptoms were monitored by a visual analog scale after each treatment period. The dose-response curves to SB revealed no signs of a reduced response to SB after any of the treatments, but significant increases in basal FEV1 and FVC were seen after the SM period (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of propranolol (0.06 mg/kg i.v.), the selective beta1-receptor antagonist metoprolol (0.12 mg/kg i.v.) and a placebo on pulmonary function, heart rate and blood pressure have been compared in asthmatics. The interaction of these drugs with increasing doses of isoprenaline on the same variables was also studied. The two beta-blockers reduced resting heart rate to the same extent, indicating the same degree of blockade of cardiac beta-receptors. Both beta-blockers reduced the basal forced expiratory volume in one second (FEV1), and the effect tended to be more pronounced after propranolol. Isoprenaline caused a dose-dependent increase in FEV1 and vital capacity (VC). These effects were almost completely blocked by propranolol, whereas after metoprolol the changes approached that of the placebo. The isoprenaline-induced increase in heart rate and fall in diastolic blood pressure was also inhibited to a considerably greater extent by propranolol than by metoprolol. The results show a selectivity of metoprolol for so-called beta1-receptors and indicate that metoprolol may be used in asthmatics provided that it is combined with beta2-receptor-stimulating drugs.

The bronchoconstrictory effect of bradykinin was studied in vivo on subjects with normal airways and on patients with airways ob struction and in vitro on isolated muscle preparations. Body plethysmographic measurements ofe airways conductance showed that bradykinin in both groups caused bronchoconstriction which probably was due to non-specific irritation of vagal irritant receptors, as it could be blocked by atropine in all but 3 obstructive patients. In these, we assume a more specific direct muscle-constricting effect from bradykinin. The in vitro tests revealed a widerange of sensitivity to bradykinin; muscles from patients with airways obstructionshowed an increased sensitivity to bradykinin.

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