Effect of mizolastine on visceral sensory afferent sensitivity and inflammation during experimental colitis

Arzneimittelforschung. 1998 Feb;48(2):179-84.

Abstract

In the present study the effect of mizolastine (CAS 108612-45-9, SL85.0324-00) a novel potent histamine H1-receptor antagonist, on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis, a rat model of inflammatory bowel disease, was investigated to determine whether mizolastine has anti-inflammatory properties. Treatment with TNBS resulted in increased nociception in response to rectal balloon distension and caused intestinal damage, tissue oedema and inflammation. Oral mizolastine (0.03-3.00 mg/kg given 1 h before and once daily for 3 days after TNBS treatment) significantly (p < 0.05) reduced nociception (49% at 0.3 mg/kg), gross intestinal damage (78% at 3.0 mg/kg), histological damage (54% at 3.0 mg/kg), intestinal tissue weight (69% at 3.0 mg/kg) and myeloperoxidase activity (66% at 3.0 mg/kg). In contrast, the H1-receptor antagonist terfenadine tested under the same experimental conditions at 3-30 mg/kg was without significant effect. It is concluded that, in addition to its antiallergic properties, mizolastine possesses anti-inflammatory actions that may not be related to its H1-receptor blocking properties, reducing sensory afferent hypersensitivity, damage and neutrophil infiltration observed during colitis.

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology*
  • Benzimidazoles / therapeutic use
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / pathology
  • Colon / pathology
  • Histamine H1 Antagonists / pharmacology*
  • Histamine H1 Antagonists / therapeutic use
  • Hypersensitivity / drug therapy
  • In Vitro Techniques
  • Male
  • Neurons, Afferent / drug effects*
  • Organ Size / drug effects
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Terfenadine / pharmacology
  • Terfenadine / therapeutic use
  • Trinitrobenzenesulfonic Acid

Substances

  • Benzimidazoles
  • Histamine H1 Antagonists
  • mizolastine
  • Terfenadine
  • Trinitrobenzenesulfonic Acid
  • Peroxidase