Effect of mizolastine on visceral sensory afferent sensitivity and inflammation during experimental colitis.
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.
Goldhill
J
J
Synthélabo Recherche, Rueil-Malmaison France.
Pichat
P
P
Roome
N
N
Angel
I
I
Arbilla
S
S
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology; D006634:Histamine H1 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006967:Hypersensitivity / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016593:Terfenadine / Q000494:pharmacology / Q000627:therapeutic use; D014302:Trinitrobenzenesulfonic Acid
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; C076170:mizolastine; D016593:Terfenadine; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase