Bronchodilation by an inhaled VPAC(2) receptor agonist in patients with stable asthma.

Abstract

BACKGROUND:

The synthetic vasoactive intestinal peptide (VIP) analogue Ro 25-1553 is a selective VIP-PACAP type 2 (VPAC(2)) 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 beta(2) 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, FEV(1)) after inhalation of Ro 25-1553 (100 microg or 600 microg) and formoterol (4.5 microg), respectively. Putative side effects were characterised by monitoring sitting blood pressure, serum potassium, electrocardiography and echocardiography.

RESULTS:

Inhalation of 600 microg Ro 25-1553 caused a rapid bronchodilatory effect (geometric mean increase in FEV(1) 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 microg 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 VPAC(2) receptor agonist constitutes a promising approach for bronchodilation in patients with asthma.

• Authors: A Lindén, L Hansson, A Andersson, M Palmqvist, P Arvidsson, C-G Löfdahl, P Larsson, J Lötvall
• Journal: Thorax (Thorax) Vol. 58 Issue 3 Pg. 217-21 (Mar 2003) ISSN: 0040-6376 [Print] England
• PMID: 12612296 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Asthmatic Agents
• Bronchodilator Agents
• Peptides, Cyclic
• Ro 25-1553
• Vasoactive Intestinal Peptide

Topics

• Administration, Inhalation
• Adult
• Aged
• Anti-Asthmatic Agents (administration & dosage)
• Asthma (drug therapy)
• Bronchodilator Agents (administration & dosage)
• Cross-Over Studies
• Double-Blind Method
• Forced Expiratory Volume (drug effects)
• Humans
• Male
• Middle Aged
• Peptides, Cyclic (administration & dosage)
• Vasoactive Intestinal Peptide (administration & dosage, analogs & derivatives)