Pharmacological examination of decongestant activity of phenylephrine in the porcine isolated nasal artery: homeopathy hidden in plain sight?

A. Abdulrahman. univercity of nottingham, Birmingham, United Kingdom.

Introduction: Phenylephrine (PHE) and pseudoephedrine (PSE) are a widely used orally-active nasal decongestants, yet the clinical efficacy of the former has been questioned¹. Our previous study, showed that 10nM PHE and even increasing the concentration by 10-folds (100nM) failed to either contract the splenic artery or enhance noradrenergic contractions, while PSE at concentrations known to occur in vivo (3μM) enhanced electrically-evoked responses². To confirm these results, we compared the actions of PHE and PSE on the porcine isolated nasal artery (PNA).

Methods: The PNA was dissected from snouts, stored overnight at 4°C in Krebs-Henseleit buffer solution which had been pre-gassed with 95% O₂/5% CO₂, The following day, fine dissection of 5mm ring segments prepared for contraction-based studies using isometric tension recording. After responses to 60mM KCl, cumulative concentration response curves to PHE (30nM-100μM; Sigma-Aldrich) and PSE (1-100μM; Sudafed syrup) were generated. Preparations were also electrically field stimulated (EFS, 4Hz, 30s, 300mA at 10min intervals) and exposed to PHE (10 &100nM) and PSE (0.3 & 3μM) for 60min. All values were expressed as the mean ± standard error of the mean (sem) in tissues from different animals (n).

Results: PHE (0.5-20μM) caused concentration-dependent contractions in the PNA (pD₂ - 5.95±0.05, n=7) with a maximum response equivalent to 60.1±8.4% of the response to 60mM KCl. In contrast, 1-100μM PSE was inactive (< 5% of the response to 60mM KCl). EFS at 4Hz, 30s produced a contraction (39.5±3.7% of 60mM KCl) that was significantly enhanced by 50.5±5.3% (p<0.05, n=5) and increased in duration (203.3±33.7%, n=5) in the presence of 3μM PSE. In contrast 10nM or 100nM PHE failed to increase either the magnitude or duration of EFS. All results were collected and analysed with ANOVA and post hoc Dunnett’s Test.

Conclusion: PHE (10nM and 100nM) failed to produce either a contraction of the PNA or enhancement in the noradrenergic responses, while PSE (3μM) enhanced noradrenergic contractions. These findings attest to the general safety of oral PHE (12mg) medication in man, but provide no pharmacological basis for the claimed efficacy as a decongestant.

References:

1. Horak F et al., (2009) Ann. Allergy Asthma Immunol 102: 116-120.

2. Abdulrahman A et al., (2017) BPS Winter Meeting.