Anti-bronchoconstrictor activities and side effect potential of inhaled formoterol and (S,R)-epiformoterol in the rhesus monkey

In a recent patent, the (S,R) isomer of epiformoterol was claimed to be a bronchodilator with reduced adverse effects compared to racemic formoterol. We initiated the present study to seek direct evidence for the claim. Anaesthetised, spontaneously breathing rhesus monkeys were set up for measuring airways resistance. Blood pressure and heart rate were measured concomitantly to gauge systemic exposure and the potential for side effects. Formoterol, 1.2µg/kg, administered by aerosol, induced rapidly developing, sustained inhibition of the bronchoconstrictor responses to aerosolised methacholine accompanied by tachycardia. (S,R)‐epiformoterol, 63µg/kg, induced anti‐bronconstrictor effects and an associated tachycardia, which were superimposable with those induced by racemic formoterol at 1.2µg/kg. Thus, (S,R)‐epiformoterol is a long‐acting anti‐bronchoconstrictor agent in the rhesus monkey and causes an associated tachycardia. This profile is not qualitatively different from that of racemic formoterol but does differ from that of salmeterol, which, in this model, shows lower efficacy and more pronounced tachycardia for an equivalent degree of anti‐bronchoconstrictor activity. Thus, the claim that (S,R)‐epiformoterol shows bronchodilator activity with reduced adverse effect potential compared to racemic formoterol is not supported by the present data. Drug Dev. Res. 57:1–5, 2002. © 2002 Wiley‐Liss, Inc.