Oxymetazoline ototoxicity in a chinchilla animal model.

OBJECTIVE: To investigate possible ototoxic effects of a one-time application of oxymetazoline drops in a chinchilla animal model with tympanostomy tubes. Study Design. A prospective, controlled animal study. SETTING: The Research Institute of the Montreal's Children Hospital, McGill University Health Centre. SUBJECTS AND METHODS: Ventilation tubes were inserted in both ears of 12 animals. One ear was randomly assigned to receive oxymetazoline drops (0.5 mL). The contralateral ear did not receive any drops, serving as a control ear. OUTCOME MEASURES: Distortion product otoacoustic emissions were measured bilaterally for a wide range of frequencies (between 1 and 16 kHz) before and 1 day after the application of oxymetazoline in the experimental ears. Two months later, the animals were sacrificed and all cochleae were dissected out and processed for scanning electron microscopy. RESULTS: In this established chinchilla animal model, the measured distortion product otoacoustic emission amplitudes and the morphological appearance on scanning electron microscopy were similar for both control and experimental ears. CONCLUSION: Oxymetazoline did not cause ototoxicity in a chinchilla animal model 2 months after a single application via a tympanostomy tube.

Anti-rhinovirus-specific activity of the alpha-sympathomimetic oxymetazoline.

Oxymetazoline (CAS 2315-02-8, OMZ, Nasivin) known as the active ingredient in nose drops and sprays demonstrates excellent efficacy in the treatment of rhinitis symptoms that are mainly caused by Rhinovirus infections. To elucidate possible modes of action, the antiviral activity of OMZ was studied in vitro on human pathogenic viruses. No in vitro effects were detected against enveloped RNA viruses, Parainfluenza Virus and Respiratory Syncytial Virus and against Adenovirus, a non-enveloped DNA-virus. In contrast, OMZ showed a specific inhibition of Human Rhinovirus (HRV). Analysis of production of HRV-14 and HRV-39 after treatment of infected HeLa cells using plaque-reduction assay and virus titration showed a strong dose-dependent antiviral activity of OMZ. Additional data demonstrated that OMZ did also directly affect HRV-14 infectivity in a dose-dependent manner. Analysis of a cell-protective effect of OMZ showed that pre-treatment of HeLa cells decreased virus adsorption as well as virus replication. Furthermore, OMZ induced a down-regulation of ICAM-1 expression on Tumor Necrosis Factor-alpha (TNF-alpha)-stimulated HeLa cells and human umbilical vein endothelial cells. Taken together, these results show that OMZ besides its vasoconstrictive action also possesses potent antiviral and anti-inflammatory activities. Therefore, OMZ does not only reduce rhinitis symptoms but additionally offers a causal therapeutic approach.

Use of mometasone furoate aqueous nasal spray in the treatment of rhinitis medicamentosa: an experimental study.

OBJECTIVE: We aimed to investigate, histopathologic changes in the nasal mucosa of guinea pig's after prolonged administration of oxymetazoline and the development of rhinitis medicamentosa, and the efficacy of mometasone furoate aqueous nasal spray and saline in reversing the ultrastructural changes attributable to rhinitis medicamentosa. METHODS: In the study, 24 male guinea pigs (500 to 600 gr) were used. Oxymetazolin (0.05%) was sprayed into the nasal cavities of the guinea pigs 3 times daily for 8 weeks. At the end of this period, 6 guinea pigs were killed and examined to make sure that the animals had developed rhinitis medicamentosa. The remaining guinea pigs were randomly divided into 3 groups. In the first group, one spray-puff of 0.05% mometasone furoate aqueous nasal spray (50 microg) was applied twice daily for 14 days. In the second group, saline solution (0.9% NaCl) was applied twice daily for 14 days. No treatment was performed in the third group. At the end of the treatment period, nasal mucosal changes were evaluated by light microscopy and electron microscopy. RESULTS: After oxymetazolin application for 8 weeks, the main histologic changes were edema, congestion, proliferation of subepithelial glands, and squamous cell metaplasia. After topical mometasone furoate aqueous spray application for 2 weeks, the edema fluid was found to diminish markedly. In the saline and no treatment groups, edema and congestion continued. In these groups of guinea pigs, fibrosis has been seen in the nasal mucosa. CONCLUSION: We found that mometasone furoate nasal spray was effective against experimentally induced rhinitis medicamentosa in guinea pigs. Mometasone furoate nasal spray may have value in the treatment of patients with rhinitis medicamentosa.

The effect of a benzalkonium chloride-containing nasal spray on human respiratory mucosa in vitro as a function of concentration and time of action.

Human respiratory mucosa was exposed to oxymetazoline nasal spray in varying concentrations and for varying periods of time in vitro. The drug destroyed the tissue in a concentration- and time-dependent manner. In the experiments with various concentrations of the spray, some tissue fragments retained their viability throughout the experiment. This number increased parallel to a decrease in concentrations of the test substance. All the tissue fragments exposed to undiluted nose spray underwent severe destructive alterations during the exposure period. These alterations appeared first and were most extensive in those exposed for the longest periods of time. It has previously been demonstrated that the toxic effect of oxymetazoline nasal spray in vitro is probably due to the preservative benzalkonium chloride. The apparent lack of consistency between the toxic effects of benzalkonium chloride in vitro and in vivo is discussed, with special reference to protective systems absent in vitro but present in vivo.

A new nasal decongestant, A-57219: a comparison with oxymetazoline.

2-(4-Amino-3,5-dichlorobenzyl)imidazoline hydrochloride (A-57219), has alpha 1-agonist/alpha 2-antagonist activity and was more effective and long-acting than oxymetazoline on canine nasal mucosa, in-vitro and in-vivo. Upon intranasal administration to dogs, the compound was devoid of systemic effects up to a concentration 1000 times that needed for local decongestant effect (1.65 micrograms, atomized from a 1 microgram mL-1 solution) suggesting limited mucosal absorption. After nasal administration to rats for 15 days at a concentration 1000 times greater than that required for nasal decongestion, no mucosal tissue toxicity or systemic effects were seen.