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Bronchodilation by an inhaled VPAC2 receptor agonist in patients with stable asthma
  1. A Lindén1,
  2. L Hansson2,
  3. A Andersson3,
  4. M Palmqvist1,
  5. P Arvidsson1,
  6. C-G Löfdahl2,
  7. P Larsson3,
  8. J Lötvall1
  1. 1Department of Respiratory Medicine and Allergology, Göteborg University, S-41345 Göteborg, Sweden
  2. 2Department of Respiratory Medicine and Allergology, Lund University Hospital, S-221 85 Lund, Sweden
  3. 3AstraZeneca Research & Development, S-221 87 Lund, Sweden
  1. Correspondence to:
    Dr A Lindén, Lung Pharmacology Group, Department of Respiratory Medicine & Allergology, Göteborg University, Guldhedsgatan 10A, SE-413 46 Gothenburg, Sweden;
    anders.linden{at}lungall.gu.se

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 β2 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.

  • asthma
  • pituitary adenylate cyclase-activating peptide (PACAP)
  • vasoactive intestinal peptide
  • Ro 25-1553

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