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. 2003 Mar;58(3):217–221. doi: 10.1136/thorax.58.3.217

Bronchodilation by an inhaled VPAC2 receptor agonist in patients with stable asthma

A Linden 1, L Hansson 1, A Andersson 1, M Palmqvist 1, P Arvidsson 1, C Lofdahl 1, P Larsson 1, J Lotvall 1
PMCID: PMC1746614  PMID: 12612296

Abstract

Background: The synthetic vasoactive intestinal peptide (VIP) analogue Ro 25-1553 is a selective VIP-PACAP type 2 (VPAC2) receptor agonist that causes a bronchodilatory effect in guinea pigs in vivo. The effect of Ro 25-1553 given by inhalation to patients with asthma was studied and compared with that of a long acting ß2 adrenoceptor agonist.

Methods: Twenty four patients with moderate stable asthma participated in a double blind, randomised, placebo controlled, crossover study. The primary variable was bronchodilatory effect (increase in forced expiratory volume in 1 second, FEV1) after inhalation of Ro 25-1553 (100 µg or 600 µg) and formoterol (4.5 µg), respectively. Putative side effects were characterised by monitoring sitting blood pressure, serum potassium, electrocardiography and echocardiography.

Results: Inhalation of 600 µg Ro 25-1553 caused a rapid bronchodilatory effect (geometric mean increase in FEV1 compared with placebo) within 3 minutes of 6% (95% CI 4 to 9), as did inhalation of formoterol (8% (95% CI 5 to 10)). The corresponding maximum bronchodilatory effect during 24 hours was similar for 600 µg Ro 25-1553 (7% (95% CI 4 to 10)) and the reference bronchodilator formoterol (10% (95% CI 7 to 12)). However, for both doses of Ro 25-1553 the bronchodilatory effect was attenuated 5 hours after inhalation whereas formoterol still had a bronchodilatory effect 12 hours after inhalation. Neither Ro 25-1553 nor formoterol produced any clinically relevant side effects. No drug related difference in adverse events was observed.

Conclusion: Inhalation of a synthetic selective VPAC2 receptor agonist constitutes a promising approach for bronchodilation in patients with asthma.

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Selected References

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