EFFECT OF MIZOLASTINE ON VISCERAL SENSORY AFFERENT SENSITIVITY AND INFLAMMATION DURING EXPERIMENTAL COLITIS

In the present study the effect of mizolastine (GAS 108612-45-9, SL85. 0324-00) a novel potent histamine H-1-receptor antagonist, on 2,4,6-tr initrobenzene sulphonic acid (TNBS)-induced colitis, a rat model of in flammatory bowel disease, was investigated to determine whether mizola stine has anti-inflammatory properties. Treatment with TNBS resulted i n increased nociception in response to rectal balloon distension and c aused intestinal damage, tissue oedema and inflammation. Oral mizolast ine (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/k g) and myeloperoxidase activity (66 % at 3.0 mg/kg). In contrast, the H-1-receptor antagonist terfenadine tested under the same experimental conditions at 3-30 mg/kg was without significant effect. It is conclu ded that, in addition to its antiallergic properties, mizolastine poss esses anti-inflammatory actions that may not be related to its H-1-rec eptor blocking properties, reducing sensory afferent hypersensitivity, damage and neutrophil infiltration observed during colitis.