Characterization of Anti-Inflammatory Properties and Evidence for No Sedation Liability for the Novel Antihistamine SUN-1334H

Abstract

Background: The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called ‘safe’ antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol. Method: Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models. Results: Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects. Conclusions: The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.

Network and matrix analysis of the respiratory disease interactome

“…These anti-histamine drugs also have anti-inflammatory properties, revealed by seven drugs having links to IL4, four having links to IL5, and four having links to IL8. This is supported by a study that shows various anti-histamines having anti-inflammatory properties in rhinitis pathology [36]. …”

Effects of the Histamine 1 Receptor Antagonist Cetirizine on the Osteoporotic Phenotype in H+/K+ATPase Beta Subunit KO Mice

“…Primarily, we do not have an unequivocal proof of the effect of the chosen dosage of cetirizine in the animals. Doses below 3 mg/kg have documented effect on active cutaneous anaphylaxis in previous studies [De Vos et al, ; Inagaki et al, ; Mandhane et al, ]. Furthermore, using the body surface area normalization method [Reagan‐Shaw et al, ], the dose given corresponds to a human dosage of approximately 0.24 mg/kg, which is well above the recommended cetirizine dosage for adults.…”

Allergic rhinitis: An update on disease, present treatments and future prospects

“…Molecules with no liability for sedation, cardiovascular side effects and better antiinflammatory potential have been studied recently. For instance, SUN-1334H is one of the recently reported antihistamines under clinical development with such properties [87,88].…”